Endocrinology Quiz on Hormonal Regulation

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Questions and Answers

What is the role of ARC NPY/AgRP/GABA neurons in food intake regulation?

Regulate metabolic rates in the liver.

Secrete hormones that decrease appetite.

Promote food intake via projections to the PVN. (correct)

Inhibit food intake via projections to the PVN.

Which structure is primarily responsible for forming the anterior pituitary?

Rathke's pouch derived tissue after detachment. (correct)

Neural endoderm above the third ventricle.

Hypothalamic neuroendocrine cells.

The pituitary stalk formed from ectoderm.

Which hormone is secreted by somatotroph cells in the anterior pituitary?

Adrenocorticotropic hormone (ACTH).

Thyroid stimulating hormone (TSH).

Luteinizing hormone (LH).

Growth hormone (GH). (correct)

What do anterior pituitary cells receive through the portal veins?

Releasing and inhibiting hormones. Signup and view all the answers

What is the primary target for luteinizing hormone (LH) secreted by gonadotrophs?

Gonads. Signup and view all the answers

What are the two broad classifications of hormones?

Water-soluble and lipid-soluble hormones Signup and view all the answers

Which type of signal transduction do lipid-soluble hormones predominantly use?

Cytoplasmic and nuclear receptors Signup and view all the answers

How does autocrine signaling differ from paracrine signaling?

Autocrine signaling targets cells that produce the hormone Signup and view all the answers

What is the primary role of phospholipase C in hormone signaling?

It converts PIP2 into second messengers DAG and IP3. Signup and view all the answers

Norepinephrine is classified as which type of hormone?

Amine hormone Signup and view all the answers

What signaling mechanism involves the hormone being released into the bloodstream from a cell?

Endocrine signaling Signup and view all the answers

What condition may result from hormone excess?

Endocrine disorders Signup and view all the answers

Growth hormone primarily activates which cellular signaling pathway?

JAK-STAT signaling pathway Signup and view all the answers

What hormone is produced by melanocytes in response to ultraviolet light?

Melanocyte-stimulating hormone Signup and view all the answers

Which of the following conditions is associated with hypocortisolism?

Secondary adrenal insufficiency Signup and view all the answers

Where are the neuroendocrine cells that produce AVP and OT located?

Hypothalamic nuclei Signup and view all the answers

Which hormone secreted by the anterior pituitary is involved in thyroid function?

Thyroid-stimulating hormone Signup and view all the answers

What effect does increased blood osmolality have on AVP secretion?

Increases AVP secretion Signup and view all the answers

What structure connects the hypothalamus to the pituitary gland?

Infundibulum Signup and view all the answers

Which hormone's secretion is stimulated during labor?

Oxytocin Signup and view all the answers

What role do target gland hormones play in the hypothalamic-pituitary-axis?

Provide negative feedback to pituitary and hypothalamus Signup and view all the answers

Which nuclei of the hypothalamus are involved in regulating food intake?

Arcuate and paraventricular nuclei Signup and view all the answers

Which hormone is released by the posterior pituitary gland?

Arginine vasopressin Signup and view all the answers

Which hormone is primarily secreted by the anterior pituitary to promote growth of bones and organs?

Growth hormone (GH) Signup and view all the answers

What is the primary role of corticotropin releasing hormone (CRH) secreted by the hypothalamus?

Stimulates anterior pituitary corticotropes to release ACTH Signup and view all the answers

Which hormone-binding protein is associated with thyroid hormones (T3 and T4)?

Thyroxine-binding globulin Signup and view all the answers

What is the function of luteinizing hormone (LH) in females?

Initiates ovulation Signup and view all the answers

Which receptor type do hydrophobic hormones primarily use for signaling?

Intracellular receptors Signup and view all the answers

What hormonal function is associated with vasopressin (AVP)?

Controls renal water retention Signup and view all the answers

Which hormone primarily influences the release of thyroid-stimulating hormone (TSH) from the anterior pituitary?

Thyrotropin releasing hormone (TRH) Signup and view all the answers

Which hormone is produced by the hypothalamus to inhibit the release of several anterior pituitary hormones, including growth hormone (GH)?

Somatostatin (SST) Signup and view all the answers

Which of the following hormones is secreted by the posterior pituitary?

Oxytocin (OT) Signup and view all the answers

What effect does estrogen have on binding proteins?

Generally binds to albumin Signup and view all the answers

What is a primary function of growth hormone (GH)?

Regulation of fat and liver metabolism Signup and view all the answers

Which hormone is responsible for stimulating the release of follicle-stimulating hormone (FSH) from the anterior pituitary?

Gonadotropin releasing hormone (GnRH) Signup and view all the answers

What condition can disrupt pituitary function?

Meningitis Signup and view all the answers

Study Notes

Endocrine Function

Endocrinology is the study of glands and the hormones they secrete
Hormones are broadly classified into two groups: water-soluble and lipid-soluble hormones
Lipid-soluble hormones travel through the bloodstream to target tissues to modify functions of those organs and tissues. They can also act upon adjacent structures (paracrine function) or cells that produced them (autocrine function)
Hormone levels are regulated by other stimulating and inhibiting hormones, negative feedback, and homeostatic signals
Hormone secretion follows specific time patterns
Endocrine disorders often result from hormone excess or deficiency

Water-Soluble Hormone Structures

Norepinephrine: Amine hormone modified from the amino acid tyrosine. Hydrophilic and polar so it cannot passively cross the cell membrane. Acts on G protein-coupled receptors.
Oxytocin: Short peptide chain with nine amino acids. Hydrophilic and water-soluble. Acts on G protein-coupled receptors
Growth Hormone: Long protein chain with 190 amino acids. Hydrophilic and water-soluble. Acts on cytokine receptors. Activates JAK-STAT signaling, involving cell surface receptors, Janus kinases (JAKs), and signal transducers and activators of transcription proteins (STATs)

Lipid-Soluble Hormone Structures

Steroid hormones are modified from cholesterol. They are hydrophobic and lipid-soluble. They act upon cytoplasmic and nuclear receptors

Modes of Hormone Signaling

Endocrine: Hormone is released into the bloodstream and travels to target cells.
Autocrine: Cell has a receptor for its own hormone.
Paracrine: Hormone diffuses to neighboring cells that have a receptor for that hormone.
Neuroendocrine: Neuron synthesizes hormone, and action potentials release the hormone into blood vessels.

Cellular Mechanisms of Hormone Signaling (Hydrophilic Hormones)

Phospholipase C cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) into diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3). These function as second messengers
Adenylyl cyclase catalyzes the conversion of ATP to pyrophosphate and 3',5'-cyclic AMP (cAMP), which acts as a regulatory signal.

Cellular Mechanisms of Hormone Signaling (Hydrophobic Hormones)

Cytoplasmic and nuclear (intracellular) receptors such as HRE, hormone-response element; mRNA, messenger RNA; NR, nuclear receptor play a significant role.

Hormone-Binding Proteins

Hydrophobic hormones travel in the circulation, protected by hormone-binding proteins (usually made by the liver). This extends their half-life and keeps them in circulation until they reach target tissues
Examples include corticosteroid-binding globulin, sex steroid-binding globulin, thyroxine-binding globulin, and albumin.

Specific Hormone-Binding Protein Examples

Cortisol: Corticosteroid-binding globulin
Adrenal androgens: Albumin
Estrogen: Albumin
Progesterone: Sex hormone-binding globulin; Albumin
Testosterone: Sex hormone-binding globulin; Albumin
Thyroid hormones (T3 and T4): Thyroxine-binding globulin; Transthyretin; Albumin
Insulin-like growth factor (IGF): Six different IGF binding proteins; Albumin
Growth hormone: Growth hormone-binding protein; Albumin

Objectives for the Endocrine System Part 1: The Hypothalamus and Pituitary

Learn the hypothalamus and pituitary anatomy and pathophysiology.
Understand the relationships between the hypothalamus and the anterior and posterior pituitary.
Learn the hormones secreted by the hypothalamus, the anterior pituitary, and the posterior pituitary.
Describe the function of Somatotrophs, Gonadotrophs, Lactotrophs, Thyrotrophs, and Corticotrophs and the signals that affect them.

Major Functions of the Hypothalamus

Control of food intake, body temperature regulation, and sleep/wake cycles.
Influences autonomic function through projections to the brainstem.
Production of posterior pituitary hormones (arginine vasopressin, AVP, and oxytocin, OT).
Production of releasing and inhibiting hormones that regulate the anterior pituitary endocrine cells.
Primary hypothalamic disorders are rare, although meningitis and neoplasms can disrupt pituitary function.

Hormones of the Hypothalamus

Thyrotropin-releasing hormone (TRH): Stimulates anterior pituitary thyrotropes to release thyroid-stimulating hormone (TSH).
Somatostatin (SST): Inhibits release of several anterior pituitary hormones, including growth hormone (GH).
Gonadotropin-releasing hormone (GnRH): Stimulates anterior pituitary gonadotropes to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
Corticotropin-releasing hormone (CRH): Stimulates anterior pituitary corticotropes to release adrenocorticotropic hormone (ACTH).
Growth hormone-releasing hormone (GHRH): Stimulates anterior pituitary somatotropes to release GH.

The Pituitary

Major functions include secretion of growth hormone (GH) and prolactin (PRL) that influence target tissues.
Secretion of trophic hormones that stimulate target gland growth and hormone secretion (e.g., ACTH, TSH, LH, FSH)
Pituitary disorders can involve hormone-secreting neoplasms

Hormones of the Anterior Pituitary

List of hormones, their structure types, and major functions are detailed in the document.

Other Hormones from the Pituitary: Melanocyte-Stimulating Hormones

MSHs are a family of peptide hormones and neuropeptides (a-MSH, β-MSH, and γ-MSH) produced by cells.
Produced by cells in the pars intermedia of the anterior pituitary lobe.
Derived from proopiomelanocortin (POMC) protein.
Produced by melanocytes in skin and increase melanin synthesis in response to ultraviolet light.

Endocrine Disorders of the Hypothalamus and Pituitary

List of disorders and their specific details can be found in the document.

Hypothalamic-Pituitary-Target Gland Axes

Hypothalamic neuroendocrine cells control pituitary hormone release
Anterior pituitary cells control target gland hormone release
Target gland hormones provide negative feedback to the pituitary and hypothalamus.

The Structure of the Hypothalamus

The hypothalamus is located at the base of the brain, on each side of the midline, surrounding the third ventricle, above the pituitary gland.
Several hypothalamic nuclei interact via synaptic connections, produce peptide neurotransmitters to regulate sleep, wakefulness, nervous system function, food intake, thirst, and temperature control.
Neuroendocrine cells with axons in the pituitary stalk release pituitary-controlling hormones.

Relationship of Hypothalamus With Pituitary

The hypothalamus lies below the thalamus, along the midline at the base of the brain.
The infundibulum (pituitary stalk) connects the hypothalamus to the pituitary gland.
Blood vessels within the infundibulum receive hypothalamic hormones
Axons of vasopressin (AVP) and oxytocin (OT) neurons connect to the posterior pituitary.
The anterior pituitary contains the endocrine cells that secrete ACTH, TSH, LH, FSH, GH, and PRL.

Hypothalamic/Posterior Pituitary Hormones

Neuroendocrine cells in the paraventricular and supraoptic nuclei produce AVP and OT.
AVP secretion is stimulated by increased blood osmolality (detected by anterior hypothalamic osmoreceptors), and by hypotension and hypovolemia sensed by baroreceptors.
Angiotensin II receptors in the hypothalamus stimulate AVP secretion also cause thirst.
Oxytocin secretion is stimulated during labor and during milk let-down when lactating.

Hypothalamic Regulation of Energy Intake and Expenditure

The hypothalamic arcuate and paraventricular nuclei regulate food intake and energy expenditure, integrating both central and peripheral signals
ARC NPY/AgRP/GABA promotes food intake via projections to the PVN (acting on Y1 and Y5 receptors)
ARC POMC neurons synthesize a-MSH, which inhibits food intake when released on PVN neurons.

Hypothalamus and Pituitary Development

Oral ectoderm folds upward, forming Rathke's pouch.
Neural endoderm folds downward, below the third ventricle.
Rathke's pouch-derived tissue detaches from its origin and forms the anterior pituitary.
Neural endoderm forms the pituitary stalk and posterior pituitary.

Hypothalamus and Anterior Pituitary Regulation

Hypothalamic neuroendocrine cells project to capillary portal system of pituitary stalk
Anterior pituitary cells receive releasing and inhibiting hormones via portal veins and pituitary capillaries
Anterior pituitary cells secrete hormones into a second capillary bed within the pituitary to travel to the systemic circulation

Targets of Anterior Pituitary Hormones

List of hormones (GH, ACTH, LH, FSH, PRL, TSH), their relevant cell types, and their targets can be found in the document.

Anterior Pituitary Somatotrophs

Function: synthesize and secrete growth hormone, and acts on cell surface receptors
Regulation of GH secretion, stimulated by GH releasing hormone (GHRH), ghrelin, and stress, hypoglycemia
Inhibited by somatostatin and insulin-like growth factor-1 (IGF-1) negative feedback.
Circadian pulsatile rhythm. Highest levels are in growing children and adolescents

Growth Hormone Secretion

GH secretion is stimulated by hypothalamic GHRH and ghrelin released from the stomach mucosa
Growth hormone acts on the liver to stimulate secretion of IGF-1. IGF-1 feeds back to suppress pituitary GH secretion.
IGF-1 also stimulates hypothalamic somatostatin secretion, which inhibits GH secretion

Growth Hormone Mechanism of Action

Growth hormone receptors are cytokine-type, linked to JAK-STAT signaling, and have some direct effects in target tissues.
Stimulates liver to synthesize IGF-1 that circulates and has growth-promoting effects via insulin-type receptors
Multiple actions-bone growth, muscle growth, organ growth, and maintenance (brain, heart, kidneys, ovary, testis, fetus), anabolic, antagonizes insulin actions on glucose regulation

Somatotroph Dysfunction

Hyposomatotrophism is congenital deficiency in GH that results in growth retardation
Hypersomatotropism is frequently triggered by a GH-secreting tumor resulting in gigantism for children and acromegaly for adults. Insulin resistance, headaches, and visual changes typically occur.

Gonadotrophs

LH and FSH secretion by the pituitary are stimulated by hypothalamic gonadotropin-releasing hormone (GnRH).
GnRH stimulates LH and FSH during fetal development to support sexual differentiation. (levels decrease 2-3 months after birth)
GnRH neurons are activated at the onset of puberty by hypothalamic kisspeptin
Nocturnal GnRH pulses stimulate LH pulses which stimulate gonads to continue development and maturation of function and secondary sex characteristics.

Anterior Pituitary Lactotrophs

Synthesize and secrete prolactin (PRL).
PRL can be secreted as a monomer, dimer, or multiple units (big PRL).
Laboratory assays can be complex, and dilution of the serum is indicated for high assay levels.
PRL secretion is under tonic inhibition by dopamine secreted by arcuate neurons into the pituitary stalk.
Estrogen stimulation during pregnancy supports lactotroph proliferation in preparation for lactation.

Lactotroph Dysfunction

Hypoprolactinemia is rare and occurs alongside general pituitary damage/compression due to another pituitary adenoma
Hyperprolactinemia is common, frequently due to microprolactinomas.
Presents with amenorrhea; infertility; hypogonadism; galactorrhea; headaches.
Evaluation by PRL assay and pituitary MRI, can be managed by dopamine agonists that suppress PRL release.

Thyrotrophs

Secrete TSH, a large glycoprotein hormone.
Stimulated by hypothalamic thyrotropin-releasing hormone (TRH).
Inhibited by triiodothyronine (T3) negative feedback.
TSH deficiency can occur with general pituitary damage; isolated thyrotroph dysfunction is rare
TSH excess is rare and can be treated with somatostatin.

Posterior Pituitary: Vasopressin

Vasopressin is a small peptide hormone (9 amino acids). Acts on G protein-coupled receptors to promote renal water conservation (anti-diuresis). Higher levels also promote vasoconstriction.
Secretion is stimulated by increased blood osmolality or hypotension.
Hypofunction-diabetes insipidus-continual excretion of very dilute urine leading to hypovolemia. Can be caused by head trauma.
Desmopressin replacement.
Hyperfunction-syndrome of inappropriate ADH-Excess water retention presents with hypervolemia, dilutional hyponatremia, and danger of brain damage from critical hyponatremia. Can be caused by non-pituitary neoplasms that secrete AVP

Anterior Pituitary Corticotrophs

Function: synthesize ACTH from the precursor POMC, located in hypothalamus/pituitary/adrenal axis.
Hypothalamic corticotropin-releasing hormone (CRH) stimulates ACTH synthesis and release from pituitary.
Adrenal cortisol feeds back to inhibit hypothalamic CRH release and pituitary ACTH release.
ACTH is a growth factor for all layers of the adrenal gland, and acts directly to stimulate adrenal cortisol synthesis and secretion.

Production of ACTH

The POMC gene is expressed in anterior pituitary corticotrophs, hypothalamic intermediate lobe cells, certain hypothalamic neurons, and other brain regions.
Differential splicing allows cells to produce different final products (ACTH and β-endorphin) from the gene.
Post-translational processing in corticotrophs produces ACTH and β-endorphin for secretion.

Corticotroph and Adrenal Hypofunction

Causes for decreased cortisol levels: Pituitary damage (overgrowth of other cells, radiation, hypoxic death).
Secondary adrenal insufficiency from prolonged suppression with exogenous steroid treatments.
Primary adrenal insufficiency (e.g., Addison's disease) from autoimmune attack

Corticotroph Hyperfunction

In the normal HPA axis, hypothalamic CRH stimulates pituitary release of ACTH resulting in the stimulation of cortisol synthesis and secretion. Growth promotion of all layers of the adrenal gland takes place.
Cortisol also provides negative hypothalamic and pituitary feedback to inhibit excessive ACTH and CRH secretion
Cushing disease involves a pituitary adenoma that continually secretes supranormal amounts of ACTH, driving adrenal gland hyperplasia and excessive cortisol secretion. Negative feedback via increased cortisol inhibits hypothalamic CRH secretion, but is ineffective at reducing ACTH secretion from the tumor.

Endocrine System Part 2: The Adrenal Glands

Major functions include secretion of aldosterone, which regulates body sodium and potassium; secretion of cortisol, which prepares the body for stress and increases in response to acute stress; secretion of sex steroids; secretion of epinephrine in response to stress.
Adrenal gland disorders can involve gland failure due to autoimmune destruction or overactivity of hormone-producing cells resulting in excess hormone.

Adrenal Gland Hormone Production

Steroid production occurs in the cortical zone.
The adrenal medulla synthesizes epinephrine and norepinephrine.

Hormones of the Adrenal Glands

Adrenal cortex: Cortisol (steroid) targets many tissues e.g. liver, muscle, immune cells, has many physiological functions including metabolic, regulation, blood pressure maintenance, and immune modulation. Aldosterone (steroid) acts on kidneys to promote sodium retention and potassium excretion to maintain blood pressure levels. Androgens (dehydroepiandrosterone, DHEA, DHEA-sulfate), (steroid) act on target tissues to promote male characteristics.
Adrenal medulla: Epinephrine and norepinephrine (catecholamines) act on target tissues to increase blood pressure, blood glucose, and catabolism (active in stress responses).

Endocrine Disorders of the Adrenal Glands and of Children and Older Adults

List of disorders relating to adrenal function and consideration for children and older adults can be found in the document.

The Adrenal Gland

Postnatal development involves fetal zone shrinkage.
Cortex differentiates and matures after 2 years, dividing into three layers (zona glomerulosa, zona fasciculata, and zona reticularis).
Zona glomerulosa produces aldosterone.
Zona fasciculata produces cortisol.
Zona reticularis produces DHEA and DHEA-sulfate AFTER adrenarche (ages 6-9).
ACTH. Provides growth support to all adrenal layers and stimulates cortisol synthesis and secretion

Adrenal Steroid Production

Cholesterol and pregnenolone are precursors of all steroid hormones.
different layers of adrenal layers have varying enzymes, leading to production of different hormones
Enzymes A and B are necessary in the synthesis of cortisol and aldosterone

Aldosterone

Aldosterone is a steroid hormone that acts on intracellular receptors. It is secreted in response to: angiotensin II; hyperkalemia.
Primary action involves the kidneys nephron collecting ducts, by stimulating Na+/K+ pump activity and apical Na+ channels, promoting sodium reabsorption, and potassium secretion.

Aldosterone Dysfunction

Hypoaldosteronism is caused by autoimmune destruction of adrenal cortex (can also occur in congenital adrenal hyperplasia).
Can be life-threatening due to sodium loss and potassium retention, and Requires replacement therapy
Hyperaldosteronism (primary aldosteronism) is caused by sodium retention, leading to volume expansion and hypertension.
Presents with headache, muscle weakness, and fatigue.

Cortisol

The primary human glucocorticoid hormone is a steroid hormone that acts via intracellular receptors.
Cytoplasmic receptors exert rapid effects. Several linking mechanisms allow cortisol to alter basal transcription machinery.

Actions of Cortisol

Cortisol has direct and permissive actions in cardiovascular, renal, metabolic, and immune function.
Prepares the body to respond to acute stress states; Promotes vascular responsiveness and capillary integrity.
Enhances liver gluconeogenesis and glycogenolysis, reduces glucose uptake, promotes hyperglycemia.
Enhances adipose release of free fatty acids; inhibits immune responses
In chronic stress, the cortisol circadian rhythm flattens, blood pressure and blood glucose increase, visceral fat increases.

Cortisol Dysfunction

Hypocortisolism is most commonly caused by Addison's disease, resulting from autoimmune adrenocortical destruction..
Managed by hormone replacement
Aldosterone deficiency-sodium deficiency, potassium excess, and hypotension
Cortisol deficiency-reduced cardiovascular function, hypotension, tachycardia; stress sensitivity; weight loss, and fatigue
ACTH excess due to loss of cortisol negative feedback occurs with increased skin pigmentation
Stress can precipitate adrenal crisis, requiring exogenous steroid coverage.

Hypercortisolism

Cushing Syndrome is due to primary adrenal hyperfunction but ACTH is low in this condition which differentiates it from Cushing disease (secondary adrenal hyperfunction)
Abdominal adiposity, facial rounding, abdominal striae, easy bruising, hypertension, and hyperglycemia are common clinical features.

Adrenal Medulla

Secretes epinephrine (80%) and norepinephrine (20%) upon stimulation by the sympathetic nervous system.
Functions as the second major stress-responsive hormone system, with cortisol.
Binds to ẞ-adrenergic receptors and a-adrenergic receptors
Increases blood pressure, heart rate, dilates bronchi, promotes liver glucose production and release, mobilizes fatty acids from adipose tissue

Adrenomedullary Dysfunction

Hypofunction is rare and has little adverse effects
Hyperfunction is generally caused by pheochromocytomas; characterized by catecholamine-secreting tumors (most are benign).
Presentation often includes episodes of hypertension, headache, profuse sweating, triggered by positions changes, exercise or urination.
Cardiovascular complications can include pulmonary edema, arrhythmias or cardiomyopathy, intracranial bleeds.
Diagnosis is based on 24-hour urine assay for catecholamine metabolites
Imaging is needed to locate the tumors.
Surgical removal is usually the definitive solution. Alpha-blockers are often used in pre-operative treatment

Pediatric Genetic Disorder

Congenital adrenal hyperplasia-Lack of the enzyme 21-hydroxylase is most common.
Results in impaired cortisol and aldosterone synthesis that disrupts steroid production. Steroid production is therefore re-routed to the production of sex steroids.
Clinical factors vary but often involve variable expression and severity. Often involves ambiguous/masculinized genitalia in females and normal genitalia in males.

Congenital Adrenal Hyperplasia

Different enzymes may be involved; severity and variable expressivity can occur.
Severe forms can present with prenatal development issues (ambiguous/masculinized genitalia in females; normal in males).
Can also involve clitoral enlargement and closure of labioscrotal folds in females

Gerontological Considerations

Endocrine alterations with aging includes decreased growth hormone and IGF-1 production ("somatopause").
Decreased DHEA and DHEAS.
Increased cortisol may contribute to hippocampal atrophy, cognitive decline, and depression.

Hormones Made by the Pancreas and Their Functions

Insulin: Protein (51 aa); targets liver, muscle, and fat; lowers blood glucose, and promotes growth (anabolic hormone)
Glucagon: Peptide (29 aa); targets the liver; raises blood glucose, is a catabolic hormone
Somatostatin (SST): Peptide (14 or 28 aa); acts locally within the pancreas, inhibiting both glucagon and insulin release

Metabolism and the Pancreas

Metabolism depends on several tissues including liver, muscle, and adipose. Primary biomolecules for energy are glucose and fatty acids.
Homeostasis involves fuel storage (primarily in the form of liver glycogen, muscle glycogen, and adipose triglyceride). Can be metabolized in both fed and fasting states.
Fasting state: fuels are mobilized by liver glycogenolysis and adipose lipolysis. Longer fasting leads to gluconeogenesis producing glucose from amino acids. Extreme starvation triggers ketogenesis that produces ketone bodies for fuel.
Anabolic hormone= insulin, levels rise in the fed state; promotes glucose storage/use, triglyceride production, inhibits glucose production.
Catabolic hormone= glucagon, levels rise in the fasting state; promotes glucose production

Type 1 Diabetes Mellitus

Autoimmune disorder, likely with a genetic component.
Marked by loss of β cells in the pancreas
Classic signs can include polyuria, polydipsia, and polyphagia and DKA
Without insulin, glucose cannot enter cells, and the body goes into a state of starvation.
Proteolysis occurs to gain amino acids, which promotes hepatic gluconeogenesis.
Lipolysis occurs to release energy in the form of fatty acids and ketone prodcution by the liver
Elevated blood glucose will be seen
Antibodies to islet proteins/cells; antibodies to glutamic acid decarboxylase (GAD), islet cell autoantigen 512 (ICA512), anti-insulin, and antibodies to tyrosine phosphatase enzymes. Islet autoantibodies can be detected prior to the development of actual disease and sometimes are found in asymptomatic family members)

Type 2 Diabetes Mellitus

Represents 95% of DM patients
Strong genetic influence; having a parent with T2DM presents with a 40% risk
Pathogenesis is insulin resistance, and insulin has reduced effectiveness at promoting muscle and adipose glucose.
Cellular mechanisms are not well-understood.
Risk factors for development of T2DM include BMI ≥25 kg/m² (or BMI ≥23 kg/m² in those with Asian ancestry); having prediabetes; history of gestational diabetes; age 45 or older.
Trajectory is marked by gradual rise of fasting blood glucose due to insulin resistance; forcing endogenous insulin secretion in an attempt to compensate. Leads to failure in the beta cells and inability to cope.

Metabolic Disorders and Associated Pathogenisis

The "ominous octet" involves tissue insulin resistance, loss of beta cell vulnerability/decreased insulin secretion, increased hepatic glucose production, increased lipolysis, reduced effectiveness of GIP and GLP-1, and increased glucagon and renal glucose reabsorption. Obesity is a significant factor and is associated with visceral fat that promotes liver insulin resistance.

Hyperosmolar Hyperglycemic Syndrome

A critical acute complication of T2DM.
Precipitation event is often infection resulting in impaired fluid intake and increased stress hormone secretion.
Hyperglycemia builds and cannot be excreted due to dehydration, so the body becomes intensely hyperosmotic
Management requires rapid fluid replacement.

Chronic Diabetes Complications

Macrovascular disease includes myocardial infarction, stroke, and peripheral arterial disease. They are attributed to dyslipidemia, inflammation, and smoking.
Inflammation is a strong contributing factor. Hypertension is frequently a risk for those with diabetes
Microvascular disease includes diabetic microangiopathy, that often targets vulnerable small vessels in the retina and kidney. Diabetic retinopathy, diabetic nephropathy, and microvascular disease combined with axonal injury can lead to diabetic neuropathy.
Chronic complications are often related to factors that can be either lifestyle related (e.g. hyperglycemia).

Chronic Microvascular Diabetes Complications

Two major hypothesis for diabetic microangiopathy: Buildup of Advanced Glycation End Products (AGEs); Increased reactive oxygen species/oxidative stress.

Gestational Diabetes Mellitus

Pathogenesis is similar to T2DM, with insulin resistance.
Chorionic somatomammotropin elevated during pregnancy acts as an anti-insulin hormone
Placenta degrades insulin, contributing more stress on β cells and increased hepatic glucose production
History of gestational diabetes is considered a significant risk factor for development of T2DM later.

Type 1 DM(continued)and Severe Diabetic Complications

Type 1 DM is marked by autoimmune disorder, which means a genetic component may play a role, as seen in the statistic of 40% concordance amongst identical twins. It presents with antibodies to islet proteins and cells, including GAD, ICA512, anti-insulin and some tyrosine phosphatase enzymes. Severe complications include DKA (Diabetic Ketoacidosis). This is a life-threatening condition of severely elevated blood glucose. Hypoglycemia is also a common, acute complication, resulting frequently from imbalance of insulin dose/food intake. Exercise can exacerbate this complication

Hypoglycemia

Most common acute complication of Type 1 diabetes (T1DM).
Can be triggered by imbalanced insulin dose/food intake.
Exercise sensitizes muscle to insulin for hours; exacerbates hypoglycemia.
Sleep reduces counterregulatory responses which can lead to increased incidents for nocturnal hypoglycemia.
Repeated hypoglycemic episodes can eventually lead to hypoglycemia unawareness and loss of epinephrine response.
Tight glucose control can often be problematic and lead to increased incidence of recurrent hypoglycemia

Other information

A number of other related topics are discussed in the document. Complete details can be found within.

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