Insulin Receptor Regulation Quiz

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Questions and Answers

What causes the insulin receptor to become less effective?

Increased insulin production

Decreased receptor density

Higher glucose sensitivity

Mutations or post-translational modifications (correct)

Which of the following is NOT associated with insulin receptor issues?

Normal receptor functionality (correct)

Mutations

Post-translational modifications

Receptor desensitization

Which of the following factors could influence the efficiency of the insulin receptor?

Dietary fat intake

Insulin levels

Environmental temperature

Genetic mutations and post-translational modifications (correct)

How do post-translational modifications affect insulin receptors?

They can alter receptor function, making it less effective Signup and view all the answers

Which statement about insulin receptor mutations is true?

They can lead to reduced receptor effectiveness Signup and view all the answers

What is a potential consequence of defects in the signaling pathways downstream of the insulin receptor?

Impairment in glucose uptake and metabolism Signup and view all the answers

Which signaling pathway is mentioned as being affected by defects downstream of the insulin receptor?

Phosphoinositide 3-kinase Pathway Signup and view all the answers

What role does the Phosphoinositide 3-kinase pathway play in cellular function?

It facilitates glucose uptake and metabolism Signup and view all the answers

Deficiencies in which aspect of the insulin signaling pathway could lead to metabolic disorders?

Phosphoinositide 3-kinase activity Signup and view all the answers

Which of the following best describes insulin's effect on glucose metabolism?

It enhances glucose uptake through signaling pathways Signup and view all the answers

What primarily causes polyphagia in individuals with insulin deficiency?

The cells' inability to utilize glucose effectively Signup and view all the answers

How does insulin deficiency directly affect hunger levels?

It prevents cells from absorbing glucose, leading to a starvation state. Signup and view all the answers

Which of the following statements about polyphagia is accurate?

It is a symptom related to the body's inability to utilize glucose. Signup and view all the answers

What underlying condition correlates with increased hunger in the presence of high blood glucose?

Insulin resistance Signup and view all the answers

In what way does the body react to high glucose levels when there is insulin deficiency?

By feeling a heightened sense of hunger Signup and view all the answers

What effect does the inhibition of adenylate cyclase activity have on cellular cAMP levels?

It decreases cAMP levels. Signup and view all the answers

Which of the following stimuli is NOT associated with the secretion of somatostatin?

Decreased amino acids. Signup and view all the answers

How does somatostatin secretion primarily modulate cellular responses?

By decreasing cAMP levels. Signup and view all the answers

What roles do increased blood glucose and amino acids play in somatostatin physiology?

They stimulate somatostatin release. Signup and view all the answers

The modulation of cellular responses by somatostatin occurs mainly through which mechanism?

Inhibition of adenylate cyclase. Signup and view all the answers

What primary factor contributes to unexplained weight loss in Type 1 diabetes?

The body breaking down fat and muscle for energy Signup and view all the answers

Which symptom is commonly associated with Type 1 diabetes aside from weight loss?

General tiredness or lack of energy Signup and view all the answers

How does the body compensate for the lack of insulin in Type 1 diabetes?

By utilizing fat and muscle for energy Signup and view all the answers

Which of the following is NOT a consequence of insufficient insulin in the body?

Increased muscle mass Signup and view all the answers

What is the result of the body breaking down fat and muscle due to lack of insulin?

Unexplained weight loss and fatigue Signup and view all the answers

What fasting blood glucose level is indicative of diabetes?

126 mg/dL (7.0 mmol/L) Signup and view all the answers

Which of the following is the criteria for a positive Oral Glucose Tolerance Test (OGTT)?

2-hour glucose ≥ 200 mg/dL (11.1 mmol/L) Signup and view all the answers

What is a primary effect of inefficient glucose utilization?

Decreased energy production Signup and view all the answers

Which statement accurately describes the consequences of decreased energy production from glucose utilization?

Fatigue and lethargy Signup and view all the answers

At what blood glucose concentration is an individual diagnosed as having diabetes based on the fasting blood glucose test?

126 mg/dL (7.0 mmol/L) Signup and view all the answers

Study Notes

Endocrine Pancreas

The pancreas has both exocrine (digestive) and endocrine (hormonal) functions.
The endocrine portion consists of Islets of Langerhans.
Islets of Langerhans contain hormone-secreting cells.
A cells (25%) secrete Glucagon.
B cells (60%) secrete Insulin and Amylin.
D cells (10%) secrete Somatostatin.
F cells secrete Pancreatic Polypeptide.

Glucose Transporters

Secondary active transport (Na+-Glucose cotransport) - SGLT1 & SGLT2, increases glucose absorption in the intestine and kidney tubules.
Facilitated diffusion via GLUTs (Na+ independent) - GLUT 1, 2, 3, 4, 5, 6, 7.
GLUT1: Basal glucose uptake in the placenta, brain, RBC, colon, kidney, and other organs. Acts as a glucose sensor in pancreatic β cells.
GLUT2, 3: Similar to GLUT1, basal glucose uptake in different tissues. GLUT4 is insulin-stimulated glucose uptake in skeletal & cardiac muscle, adipose tissue, and other tissues.
GLUT5 facilitates fructose transport.
GLUT6 acts as a pseudogene.
GLUT7 increases glucose 6-phosphate transport into the endoplasmic reticulum (hepatic and other tissues).

Insulin

Insulin is a protein hormone composed of two chains linked by disulfide bonds.
It is synthesized as Preprohormone.
During packaging in granules by the Golgi, proinsulin is cleaved into insulin and C peptide.
C peptide has no biological activity but is secreted in equimolar ratio with Insulin. Its concentration in plasma reflects β-cells activity.
Insulin is degraded by the enzyme Insulinase in the liver and kidneys, to a lesser extent in the muscles.

Regulation of Insulin Secretion

Stimulators: Serum glucose, amino acids, free fatty acids, serum ketone bodies, hormones (e.g., GIP, Glucagon, Gastrin, Cholecystokinin, CCK, Secretin, VIP, Epinephrine (β-receptor), parasympathetic nervous system stimulation).
Inhibitors: Low glucose, amino acids, free fatty acids, hormones (e.g., Somatostatin, Epinephrine (α-receptor)), sympathetic nervous system stimulation.
A normal human secretes ~40U of insulin per day.
Insulin secretion increases ~5-10 folds following food ingestion.

Mechanism of Glucose-Induced Insulin Secretion

Glucose enters β-cells, increasing metabolism, leading to ATP production.
Increased ATP closes ATP-sensitive K+ channels (KATP channels).
Membrane depolarizes.
Voltage-gated calcium channels open.
Calcium influx triggers insulin exocytosis.

Insulin Binding & Signal Transduction

Insulin binds to insulin receptor → autophosphorylation of receptor tyrosine residues.
This activates various intracellular signaling pathways primarily: PI3K (Phosphoinositide 3-kinase) Pathway (translocates GLUT4 transporters to cell membrane for glucose uptake) and MAPK (Mitogen-Activated Protein Kinase) Pathway (growth and differentiation).

Mechanism of Insulin Action

Insulin binds to its receptor → phosphorylation of enzymes (like IRS).
Stimulates glucose transport, protein synthesis, and fat synthesis and inhibits glucose synthesis.

Insulin Target Tissues and Exceptions

Target tissues for insulin are adipose tissue and muscle.
Brain (except hypothalamus), RBCs, kidney tubules, intestinal mucosa, lens of the eye and β-cells of pancreas, liver and brain primarily use GLUT1, 2 &/or 3; these tissues are independent of insulin for glucose uptake.

In Muscles

Under resting conditions, glucose uptake is dependent on GLUT-4.
In moderate or severe exercise, special GLUT-4 vesicles move into the cell membrane only when activated by exercise, it is not dependent on insulin.

Liver

Liver does not use GLUT-4. Instead glucose enters the liver along its concentration gradient.
Hexokinase and glucokinase phosphorylate glucose to glucose-6-phosphate.
Glucose-6-phosphate is trapped inside liver cells.
Thus, intracellular free glucose decreases compared to extracellular free glucose.
Glucose continues to diffuse into the liver cells along the concentration gradient.

Physiological Actions of Insulin

Carbohydrate Metabolism: Promotes glucose storage as glycogen, inhibits glycogenolysis and gluconeogenesis in the liver. Muscle cells take up glucose from the blood and store it as glycogen.
Protein Metabolism: Promotes amino acid entry into muscle cells and promotes protein synthesis in ribosomes. Inhibits proteolysis by decreasing lysosomal activity.
Fat Metabolism: Promotes fat storage, inhibits lipolysis, and promotes lipogenesis (fatty acid and triglyceride synthesis) in adipocytes.

Glucagon

Glucagon is a peptide hormone produced by alpha cells of the pancreas.
Glucagon synthesis: Preproglucagon → Proglucagon → Glucagon
Mechanism of Action: Glucagon binds to glucagon receptors on target cells (primarily in the liver) → activation of adenylate cyclase → increasing cAMP levels initiating metabolic changes.

Regulation of Glucagon Secretion

Stimulators: Low blood glucose, high amino acid levels, sympathetic nervous system stimulation.
Inhibitors: High blood glucose, insulin, somatostatin.

Physiological Effects of Glucagon

Promotes glycogenolysis (breakdown of glycogen) in the liver.
Promotes gluconeogenesis (producing glucose from non-carbohydrate sources) in the liver.
Promotes lipolysis and ketone body formation (ketogenic effect).

Mechanism of Glucagon Action on Cells (Fasting State)

Low plasma glucose level stimulates glucagon release increasing glycogenolysis, gluconeogenesis and lipolysis to maintain plasma glucose level.
Prolonged hypoglycemia leads to glucagon dominance. This increases production of glucose from non-carbohydrate sources and from fatty acids (ketones); this maintains blood glucose level for brain & peripheral tissues.

Somatostatin

Somatostatin is a peptide hormone produced primarily in the delta cells of the pancreas and hypothalamus.
Mechanism of Action: Binds to somatostatin receptors in various tissues → inhibits adenylate cyclase activity → Decreasing cAMP levels modulating cellular responses.

Regulation of Somatostatin Secretion

Stimulators: Increased blood glucose, amino acids, fatty acids.
Negative feedback: Functions as a regulatory mechanism to prevent excessive hormone release, preventing excessive release of growth hormone, insulin, glucagon, and gastrointestinal hormones.

Pancreatic Polypeptide

Pancreatic polypeptide (PP) is a peptide hormone secreted by F cells (also known as PP cells) of the pancreas.
Stimuli for secretion include food intake (especially protein-rich meals), exercise and some gastrointestinal hormones.
Physiological effects include inhibiting both exocrine and endocrine pancreatic secretions (particularly insulin and glucagon), slowing gastric emptying, decreasing gastric acid secretion potentially affecting appetite and food intake.

Insulin Resistance

A condition in which the body's cells become less responsive to insulin, which plays a crucial role in regulating blood sugar.
Contributing factors: Obesity, physical inactivity, a diet high in refined carbohydrates and unhealthy fats.
Mechanisms of insulin resistance may include impaired signaling pathways downstream of the insulin receptor, chronically low-grade inflammation (often associated with obesity), or increased levels of free fatty acids and lipid intermediates.

Diabetes Mellitus (DM)

A chronic metabolic disorder characterized by high blood glucose levels due to insulin deficiency, resistance, or both.
Abnormalities in carbohydrate, protein and fat metabolism result.

Types of DM

Type 1: Autoimmune destruction of beta cells, usually in childhood and teens, requiring insulin therapy
Type 2: Insulin resistance and/or impaired pancreatic insulin secretion, often in adulthood, responsive to lifestyle changes or oral hypoglycemics.
Gestational: develops during pregnancy, often resolves after delivery
Definition: Glucose level in urine more than renal threshold (180 mg%).

Cardinal Signs of DM

Polyuria: Increased urination due to excess glucose in urine drawing water.
Polydipsia: Increased thirst due to dehydration caused by polyuria.
Polyphagia: Increased hunger due to cells inability utilize glucose effectively due to insulin resistance or deficiency.
Unexplained Weight Loss: Body breaks down fat and muscle for energy due to lack of insulin.
Fatigue: Inefficient glucose utilization leads to energy production decrease, causing fatigue.

Diagnosis of Diabetes Mellitus

Fasting blood glucose test ≥ 126 mg/dL (7.0 mmol/L).
Oral glucose tolerance test with a 2-hour glucose level ≥ 200 mg/dL (11.1 mmol/L).
HbA1c test ≥ 6.5% indicates poor long-term glucose control.

Management of Diabetes Mellitus

Lifestyle Modifications: Diet, exercise, weight management.
Pharmacological Treatments: Insulin therapy for Type 1, or oral hypoglycemics (and insulin) for Type 2.
Monitoring: Regular blood glucose and HbA1c checks.

Acute Complications of DM

Diabetic Ketoacidosis (DKA): Mostly seen in type 1 DM, characterized by nausea, vomiting, abdominal pain, rapid breathing, and fruity breath. (high blood sugar).
Hyperglycemic Hyperosmolar State (HHS): Primarily in Type 2 DM, characterized by severe dehydration, confusion, and high blood sugar levels.

Chronic Complications of DM

Microvascular Complications (affects small blood vessels): Diabetic retinopathy (vision problems), nephropathy (kidney disease), and neuropathy (nerve damage).
Macrovascular Complications (affects large blood vessels): Cardiovascular disease (risk of heart attack, stroke), and peripheral artery disease (poor circulation in limbs).

Insulin Excess

Hyperinsulinemia: Abnormally high level of insulin in the blood, often in relation to blood glucose levels.
Causes: Insulinoma (rare tumor), reactive hypoglycemia (excessive insulin release after high-carbohydrate meal), obesity (insulin resistance and compensatory hyperinsulinemia), medications (e.g., sulfonylureas).
Symptoms: At levels below 1.2-1.8 mmol/l; hunger, confusion, lethargy, convulsions, coma, and eventually death.

Management Strategies for Insulin Excess

Dietary Adjustments: Reduce carbohydrate intake.
Physical Activity: Regular exercise.
Medical Interventions: In cases like insulinomas, surgical removal may be necessary; medications may be used to regulate insulin levels.

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Description

Test your knowledge on insulin receptor effectiveness and the factors affecting it. This quiz covers mutations, signaling pathways, and metabolic disorders related to insulin signaling. Understand the implications of insulin deficiency and its relation to hunger and glucose metabolism.