Endocrine Pancreas PDF

‫‪Endocrine pancreas‬‬ ‫أد‪.‬بان جابر عيدان‬ ‫دكتوراه في فسلجة العقم‬ ‫بكالوريوس طب وجراحة عامة‬ ‫دبلوم عالي في النسائيه والتوليد‬ Pancreas It situated behind the stomach, the pancreas has both exocrine (digestive) and  endocrine (hormonal) func...

‫‪Endocrine pancreas‬‬ ‫أد‪.‬بان جابر عيدان‬ ‫دكتوراه في فسلجة العقم‬ ‫بكالوريوس طب وجراحة عامة‬ ‫دبلوم عالي في النسائيه والتوليد‬ Pancreas It situated behind the stomach, the pancreas has both exocrine (digestive) and  endocrine (hormonal) functions. Islets of Langerhans: The endocrine portion consists of small clusters of cells known as the islets of Langerhans, which contain various hormone-secreting cells. Insulin Insulin is a protein hormone composed from two chains linked by disulfide bonds. It synthesized as Preprohormone During packaging in granules by golgi, proinsulin is cleaved into insulin and C peptide. C peptide had no biological activity, but secreted in equimolar ratio with Insulin , Hence its concentration in plasma directly reflects β–cells activity. Regulation of insulin secretion The amount of insulin secreted in the basal state is about 1 U/hour, with 5 - 10 folds increase following ingestion of food. The average amount secreted per day in a normal human is about 40 U. Mechanism of glucose induced insulin secretion Insulin Binding Receptor Interaction: Insulin binds to the insulin receptor, which is a transmembrane protein found on the surface of target cells (like muscle and adipose tissue). Receptor Type: The insulin receptor is a type of receptor tyrosine kinase.  Signal Transduction Autophosphorylation: Binding of insulin causes autophosphorylation of tyrosine residues on the receptor. Downstream Signaling: This activates various intracellular signaling pathways, primarily: ◦ The PI3K (Phosphoinositide 3-kinase)Pathway: Leads to the translocation of GLUT4 transporters to the cell membrane, facilitating glucose uptake. ◦ MAPK (Mitogen-Activated Protein Kinase)Pathway: Involved in cellular growth and differentiation. Mechanism of action insulin Insulin (within seconds-hours) increases the entrance of glucose to most of the cells of the body but not to the:  Brain (except hypothalamus). The brain cells are permeable to glucose and can use glucose without the intermediation of insulin. Neurons use only glucose for energy.  RBCs, kidney tubules, intestinal mucosa, lens of the eye, and β-cells of pancreas, liver and brain, do not require insulin for efficient uptake of glucose. This is because these organs don't use GLUT4 for importing glucose but use different transporters (GLUT- 1, 2 &/or 3, (insulin- independent transporter) located permanently in the plasma membrane.  The target tissues of insulin are adipose tissue, and muscles In muscles : Physiological actions of insulin Insulin is an anabolic hormone and its net effect is storage of carbohydrates, proteins and fat. Therefore, it is called Hormone of Abundance. 1.On carbohydrate metabolism : a. liver Promotes glucose storage as glycogen Inhibits glycogenolysis Inhibits gluconeogenesis b. muscle Stimulates glucose uptake (GLUT4) Promotes glucose storage as glycogen c. adipose tissue Stimulates glucose transport into adipocytes Promotes the conversion of glucose into triglycerides and fatty acids “ANTI-DIABETOGENIC” 2. On protein metabolism Facilitates amino acids entry into muscle cell Facilitates protein synthesis in ribosomes Inhibits proteolysis by decreasing lysosomal activity “ANABOLIC HORMONE 3. On fat metabolism: a. liver Anti ketogenic & Lipogenic b. In fat cell Promotes storage of fat Inhibits lipolysis Promotes lipogenesis 4. On plasma k+ concentration Facilitates rapid entry of K+ into cell by simulating Na-K ATPase activity. Glucagon  Glucagon is a peptide hormone produced by the alpha cells of the pancreas.  Synthesis Process: Preproglucagon → Proglucagon → Glucagon  Mechanism of Action Receptor Binding: Glucagon binds to glucagon receptors on target cells (primarily in the liver). Signal Transduction: Activation of adenylate cyclase, increasing cAMP levels and initiating metabolic changes. Regulation of Glucagon Secretion Stimuli for Secretion: Low blood glucose levels, high amino acid concentrations, and sympathetic nervous stimulation. Inhibition: High blood glucose levels, insulin release, and somatostatin. Physiological actions of glucagon Metabolic Effects of Glucagon  Glycogenolysis: Stimulates the breakdown of glycogen to glucose in the liver.  Gluconeogenesis: Promotes the formation of glucose from non-carbohydrate sources.  Lipolysis: Facilitates the breakdown of fats for energy. Consequently, it increases ketone bodies formation (ketogenic effect) Glucagon Action on Cells: Dominates in Fasting State Metabolism Clinical Relevance of Glucagon Used in treating severe hypoglycemia, especially in emergency situations. Potential Therapies: Research on glucagon receptor antagonists and their role in metabolic disorders.  Somatostatin Somatostatin is a peptide hormone that inhibits the release of several other hormones. Source: Produced primarily in the delta cells of the pancreas and in the hypothalamus. Mechanism of Action Binds to somatostatin receptors found in various tissues. Inhibits adenylate cyclase activity, decreasing cAMP levels and modulating cellular responses. Regulation of Somatostatin Secretion  Stimuli for Secretion: Increased blood glucose, amino acids, and fatty acids stimulate somatostatin release.  Negative Feedback: Functions as a regulatory mechanism to prevent excessive hormone release. Physiological Effects  Inhibition of Hormone Secretion: Reduces the release of growth hormone, insulin, glucagon, and gastrointestinal hormones.  Impact on Digestion: Decreases gastric acid secretion and slows gastric emptying. Therapeutic Applications: Use of somatostatin analogs in treating various conditions (e.g., acromegaly, gastrointestinal bleeding).  Pancreatic polypeptide  A peptide hormone secreted by the F cells (also known as PP cells) of the pancreas.  It plays a role in regulating pancreatic secretions and digestive processes. Release Stimuli: Secretion is stimulated by:  Food intake (especially protein-rich meals)  exercise  Certain gastrointestinal hormones (e.g., cholecystokinin) Physiological Effects  Regulation of Pancreatic Secretion: Inhibits both exocrine and endocrine secretions from the pancreas, particularly the secretion of insulin and glucagon.  Impact on Digestion: Slows gastric emptying and decreases the secretion of gastric acid.  Role in Appetite Regulation: May have an effect on appetite and food intake, contributing to the feeling of satiety.  Potential Biomarker: Levels of PP can be altered in various conditions, including obesity and diabetes, making it a potential biomarker for these diseases. Insulin resistance  is a condition in which the body's cells become less responsive to the hormone insulin, which plays a crucial role in regulating blood sugar levels. Contributing Factors  Obesity: Adipose tissue secretes various adipokines (e.g., resistin, TNF-alpha) that can contribute to insulin resistance.  Physical Inactivity: Lack of exercise reduces glucose uptake and utilization by muscles, worsening insulin sensitivity.  Diet: High intake of refined carbohydrates and unhealthy fats can promote insulin resistance. Mechanisms of Insulin Resistance Receptor Issues: The insulin receptor may become less effective due to mutations or post-translational modifications. Intracellular Signaling: Defects in signaling pathways downstream of the insulin receptor (like Phosphoinositide 3- kinase pathway) can impair glucose uptake and metabolism. Inflammation: Chronic low-grade inflammation (often associated with obesity) can interfere with insulin signaling. Pro-inflammatory cytokines can impair insulin receptor signaling and promote insulin resistance. Lipid Accumulation: Increased levels of free fatty acids and lipid intermediates   Diabetes mellitus (DM) Definition: A chronic metabolic disorder characterized by high blood glucose levels due to insulin deficiency, resistance, or both. It may result from many environmental and genetic factors often acting jointly. These abnormalities lead to abnormalities in carbohydrate, protein and fat metabolism. Types of DM The cardinal signs of DM are: 1. Polyuria Definition: Increased urination. Mechanism: High blood glucose levels lead to excess glucose in the urine, which draws water with it, resulting in increased urine production. loss of glucose in urine. - when the blood glucose level becomes > renal threshold (180 mg%). 2. Polydipsia (Increased thirst). Mechanism: Due to dehydration caused by polyuria, the body signals for increased fluid intake to compensate for lost fluids. 3. Polyphagia (Increased hunger). Mechanism: Despite high blood glucose levels, the body's cells cannot utilize glucose effectively due to insulin deficiency or resistance, leading to a state of starvation and increased appetite. 4. Unexplained Weight Loss Mechanism: In Type 1 diabetes, the body breaks down fat and muscle for energy due to lack of insulin, resulting in weight loss. 5. Fatigue: General tiredness or lack of energy. Mechanism: Inefficient glucose utilization leads to decreased energy production, causing fatigue Diagnosis  Fasting Blood Glucose: ≥ 126 mg/dL (7.0 mmol/L).  Oral Glucose Tolerance Test: 2-hour glucose ≥ 200 mg/dL (11.1 mmol/L).  HbA1C Test: ≥ 6.5% indicates poor long-term glucose control. HbA1c :When plasma glucose is episodically elevated over time, small amounts of hemoglobin A is glycosylated by non-enzymatic pathway to form HbAlc. Level of HbAlc is an index of control of diabetes for 6 - 10 weeks before measurement. Management of Diabetes Lifestyle Modifications: Diet, exercise, weight management. Pharmacological Treatments: Insulin therapy for Type 1; oral hypoglycemics and insulin for Type 2. Monitoring: Regular blood glucose monitoring and HbA1C checks. Acute Complications Diabetic Ketoacidosis (DKA): ◦ Mostly seen in Type 1 DM. ◦ Symptoms: Nausea, vomiting, abdominal pain, rapid breathing, fruity breath. Hyperglycemic Hyperosmolar State (HHS): ◦ Primarily in Type 2 DM. ◦ Symptoms: Severe dehydration, confusion, and high blood sugar levels. Chronic Complications Microvascular Complications: Affects small blood vessels. Macrovascular Complications: Affects large blood vessels. 1.Microvascular Complications Diabetic Retinopathy:Damage to the retina leading to vision problems. Diabetic Nephropathy:Kidney damage that can lead to chronic kidney disease. Diabetic Neuropathy: Nerve damage causing pain, tingling, or loss of sensation, particularly in the feet. 2.Macrovascular Complications Cardiovascular Disease:Increased risk of heart attack and stroke. Peripheral Artery Disease: ◦ Poor circulation in the limbs leading to pain and ulcers. Insulin Excess:  Hyperinsulinemia: A condition characterized by an abnormally high level of insulin in the blood, often in relation to blood glucose levels.  Causes of Insulin Excess  Insulinoma: A rare tumor of the pancreas that secretes excess insulin.  Reactive Hypoglycemia: Occurs when insulin is released excessively in response to a high-carbohydrate meal.  Obesity: Increased fat tissue can lead to insulin resistance and compensatory hyperinsulinemia.  Medications: Certain drugs (e.g., sulfonylureas) can stimulate excessive insulin release.  At lower plasma glucose level (below 1.2-1.8 mmol/l);hypoglycemic symptoms appears including hunger, confusion, lethargy, convulsions, coma and eventually death. Management Strategies  Dietary Adjustments: Reducing carbohydrate intake can help manage insulin levels.  Physical Activity: Regular exercise can improve insulin sensitivity.  Medical Interventions: In cases like insulinomas, surgical removal may be necessary; medications may also be used to regulate insulin levels.