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Pancreatic Endocrine Function Overview

Jul 10, 2025

Overview

This lecture reviews the endocrine function of the pancreas, focusing on insulin, glucagon, and diabetes mellitus, summarizing hormone actions, regulation, feedback, and pathologies.

Pancreatic Endocrine Function

  • The pancreas has both exocrine (digestive) and endocrine (hormonal) functions.
  • Endocrine function is mainly by the islets of Langerhans, containing alpha, beta, and delta cells.
  • Alpha cells secrete glucagon; beta cells secrete insulin (and amylin); delta cells secrete somatostatin.

Insulin: Actions and Regulation

  • Insulin is secreted in response to high blood glucose and amino acids, mainly after meals.
  • Insulin promotes glucose uptake in muscle and adipose tissue, glycogen synthesis in the liver, and fat/protein storage.
  • Synthesis involves preproinsulin → proinsulin → insulin + C-peptide (C-peptide used to measure endogenous insulin).
  • Insulin acts via a membrane tyrosine kinase receptor, activating intracellular signaling for nutrient uptake and storage.
  • Insulin increases glucose, amino acid, potassium, and phosphate entry into cells.
  • Brain tissue glucose uptake is insulin-independent.
  • Insulin also inhibits protein breakdown and gluconeogenesis.
  • Insulin secretion is stimulated by glucose, amino acids, GI hormones, autonomic input, and other hormones (e.g., glucagon, GH, cortisol).

Glucagon: Actions and Regulation

  • Glucagon is secreted by alpha cells when blood glucose falls.
  • It increases blood glucose via glycogen breakdown and gluconeogenesis in the liver.
  • Glucagon promotes lipolysis in adipose tissue, providing fatty acids for energy.
  • Secretion is mainly regulated by blood glucose, but also by amino acids and sympathetic stimulation.

Somatostatin and Paracrine Interactions

  • Delta cells secrete somatostatin, which inhibits both insulin and glucagon to moderate hormone swings.
  • Pancreatic hormones have paracrine effects, regulating each other locally.

Blood Glucose Regulation

  • The liver buffers blood glucose by storing/releasing glucose as glycogen.
  • Insulin and glucagon maintain glucose within normal limits, with backup by epinephrine, cortisol, and growth hormone in hypoglycemia.
  • Both hypoglycemia and hyperglycemia have severe systemic effects, especially on the brain, kidneys, and cardiovascular system.

Diabetes Mellitus

  • Diabetes mellitus means "sweet urine" due to high blood sugar.
  • Type 1 diabetes: Insulin deficiency from beta cell destruction, usually juvenile onset, causes increased blood glucose, fat/protein breakdown, ketosis, and weight loss.
  • Type 2 diabetes: Insulin resistance (often obesity-related), initially high insulin that declines as beta cells fail; also leads to hyperglycemia and related complications.
  • Type 1 treated with insulin; Type 2 treated with weight loss, exercise, drugs to increase sensitivity/production, insulin in advanced cases.
  • Both types have increased risk of atherosclerosis, hypertension, kidney disease, and blindness.

Diagnosis and Treatment of Diabetes

  • Diagnosis: high fasting glucose, glucose in urine, glucose tolerance test, high insulin in type 2, acetone breath.
  • Treatment: insulin (type 1), lifestyle changes or oral drugs (type 2), lipid-lowering agents for cardiovascular risk.

Insulin Excess (Hyperinsulinism)

  • Hyperinsulinism (e.g., insulinoma) leads to profound hypoglycemia and CNS symptoms; treat with glucose, glucagon, or tumor removal.

Key Terms & Definitions

  • Insulin — hormone from beta cells lowering blood glucose by promoting cellular uptake and storage.
  • Glucagon — hormone from alpha cells raising blood glucose by promoting glycogen breakdown and gluconeogenesis.
  • Somatostatin — hormone inhibiting insulin and glucagon release.
  • Glycogenesis — conversion of glucose to glycogen for storage.
  • Gluconeogenesis — generation of glucose from non-carbohydrate sources.
  • Diabetes mellitus — disorder of high blood glucose due to insulin problems.

Action Items / Next Steps

  • Review the functions of pancreatic endocrine cells.
  • Know insulin and glucagon mechanisms and their effects.
  • Complete end-of-chapter questions:
    • Which cells secrete insulin and glucagon?
    • What type of receptor is the insulin receptor?
    • Name three causes of insulin resistance and the diabetes type they cause.

Certainly! Here's a highly detailed, expanded bullet-point summary using the exact wording from the video, with added depth and clarity:

Pancreatic Endocrine Function

  • The pancreas has both digestive (exocrine) and endocrine functions; today’s focus is on the endocrine function.
  • The two main hormones secreted by the pancreas are insulin and glucagon, which regulate glucose, lipid, and protein metabolism to maintain homeostasis.
  • Other hormones secreted include amylin, somatostatin, and pancreatic polypeptides, but these play lesser roles in this chapter.
  • The pancreas is divided into two tissue groups:
    • Acini: secrete digestive enzymes.
    • Islets of Langerhans: contain endocrine cells.
  • Within the islets of Langerhans, there are three main cell types:
    • Alpha cells: secrete glucagon.
    • Beta cells: secrete insulin and amylin.
    • Delta cells: secrete somatostatin.
  • These hormones have paracrine effects, meaning they influence each other locally:
    • Insulin inhibits glucagon.
    • Amylin inhibits insulin.
    • Somatostatin inhibits both insulin and glucagon.
  • This interaction allows one hormone’s secretion to inhibit the others, enhancing the overall effect.

Insulin: Synthesis and Secretion

  • Insulin is secreted when there is an abundance of energy, mainly after meals when blood glucose is high.
  • Insulin’s main role is to package energy away by moving glucose, fats, and proteins from the bloodstream into cells for storage.
  • Insulin synthesis in beta cells:
    • Ribosomes produce preproinsulin.
    • Preproinsulin is cleaved in the endoplasmic reticulum to proinsulin (containing A, B, and C peptides).
    • The Golgi apparatus chops off the C-peptide, producing active insulin.
    • Insulin and C-peptide are packaged into secretory granules.
  • Measuring C-peptide levels can indicate endogenous insulin production, useful in diabetes management.
  • Insulin is not protein-bound in blood, so it is rapidly degraded (half-life ~6 minutes) by insulinase in the liver.

Insulin: Mechanism of Action

  • Insulin acts via a tyrosine kinase enzyme-linked receptor on the cell membrane.
  • Activation of this receptor phosphorylates intracellular enzymes, leading to:
    • Increased glucose uptake into muscle and adipose cells.
    • Increased permeability to amino acids, potassium, and phosphate ions.
    • Activation of metabolic enzymes for glycogen synthesis.
    • Increased transcription and translation of proteins over time.
  • The brain is insulin-independent for glucose uptake, ensuring constant glucose supply.
  • Muscle cells:
    • Increase glucose uptake and glycogen storage when insulin is present.
    • Cannot uptake glucose during fasting (no insulin), relying on fatty acid metabolism or stored glycogen.
    • During heavy exercise, muscle contraction increases glucose uptake via GLUT4 transporters, independent of insulin.
  • Liver cells:
    • Insulin promotes glucose uptake by increasing glucokinase activity, trapping glucose inside cells.
    • Insulin inhibits phosphorylase, preventing glycogen breakdown.
    • Insulin activates glycogen synthase, promoting glycogen formation.
    • During fasting (no insulin), these effects reverse, and the liver releases glucose via glycogenolysis and gluconeogenesis.

Insulin: Effects on Fat and Protein Metabolism

  • Fat metabolism:
    • Insulin promotes fat synthesis and storage by converting excess glucose into fatty acids in the liver.
    • Fatty acids are converted into triglycerides and transported to adipose tissue via lipoproteins.
    • Insulin activates lipoprotein lipase to break down triglycerides for adipose uptake.
    • Insulin inhibits hormone-sensitive lipase in adipose tissue, preventing fat breakdown.
    • Insulin promotes glucose uptake into fat cells, enhancing fat storage.
  • Without insulin:
    • Increased fat breakdown releases fatty acids and glycerol into the bloodstream.
    • The liver converts excess fatty acids into cholesterol and phospholipids, increasing lipoproteins and risk of atherosclerosis.
    • Fatty acids are converted into ketone bodies (acetoacetic acid), leading to ketoacidosis, which can cause coma and death.
    • Ketones cause a characteristic sweet breath odor.
  • Protein metabolism:
    • Insulin increases amino acid uptake into cells, promoting protein synthesis.
    • It inhibits protein catabolism and gluconeogenesis (conversion of amino acids to glucose).
    • Without insulin, protein breakdown increases, leading to muscle wasting, increased amino acids in blood, increased gluconeogenesis, and increased urea excretion.
    • This results in weakness and organ dysfunction.

Regulation of Insulin Secretion

  • The primary stimulus for insulin secretion is blood glucose concentration.
  • Glucose enters beta cells via GLUT2 transporters, is metabolized to produce ATP.
  • Increased ATP closes potassium channels, causing cell depolarization.
  • Depolarization opens calcium channels, allowing calcium influx.
  • Increased intracellular calcium triggers exocytosis of insulin.
  • Insulin secretion is biphasic:
    • First phase: rapid release of preformed insulin.
    • Second phase: sustained secretion as new insulin is synthesized.
  • Insulin secretion increases with rising glucose and plateaus at high glucose levels.
  • Other stimulators of insulin secretion (supplementary to glucose):
    • Amino acids (synergistic with glucose).
    • Gastrointestinal hormones (gastrin, cholecystokinin) — anticipatory increase during eating.
    • Glucagon (paradoxically increases insulin to prevent glucose roller coaster).
    • Growth hormone, cortisol, progesterone, estrogen (can antagonize insulin effects).
    • Parasympathetic nervous system (rest and digest) stimulates insulin secretion.
  • Sympathetic nervous system inhibits insulin secretion to maintain glucose availability during stress.

Glucagon: Actions and Regulation

  • Secreted by alpha cells when blood glucose falls.
  • Glucagon increases blood glucose by:
    • Activating adenyl cyclase → cAMP → protein kinase cascade.
    • Activating phosphorylase a, promoting glycogen breakdown in the liver.
    • Stimulating gluconeogenesis in the liver.
  • Glucagon promotes lipolysis in adipose tissue, increasing fatty acids for energy.
  • Other effects include enhancing heart strength, increasing blood flow, promoting bile secretion, and inhibiting gastric acid secretion.
  • Glucagon secretion is stimulated by:
    • Low blood glucose.
    • Amino acids.
    • Sympathetic stimulation (beta-adrenergic).

Somatostatin and Paracrine Regulation

  • Secreted by delta cells.
  • Somatostatin inhibits secretion of both insulin and glucagon, moderating hormone swings.
  • It decreases gastrointestinal motility and secretion, prolonging nutrient absorption.
  • Somatostatin from the hypothalamus also inhibits growth hormone release.

Blood Glucose Homeostasis

  • The liver acts as a buffer by storing glucose as glycogen when blood glucose is high and releasing glucose when low.
  • Insulin and glucagon provide feedback control to maintain blood glucose within normal limits.
  • Backup systems during severe hypoglycemia include epinephrine, growth hormone, and cortisol.
  • Both hypoglycemia and hyperglycemia have serious systemic effects:
    • Hypoglycemia affects brain function.
    • Hyperglycemia causes cellular dehydration, increased urination, ketoacidosis, atherosclerosis, hypertension, kidney disease, and blindness.

Diabetes Mellitus

  • Means "sweet urine" due to glucose in urine.
  • Type 1 diabetes:
    • Insulin-dependent; caused by autoimmune destruction of beta cells.
    • Usually juvenile onset (~14 years).
    • Characterized by insulin deficiency, hyperglycemia, fat and protein breakdown, ketosis, weight loss.
  • Type 2 diabetes:
    • Non-insulin dependent; caused by insulin resistance.
    • Usually adult onset, often associated with obesity.
    • Initially high insulin levels due to resistance; beta cells may become exhausted over time.
    • Similar complications as type 1.
  • Causes of insulin resistance include obesity, excessive glucocorticoids (Cushing’s syndrome, steroids), acromegaly, pregnancy (gestational diabetes), polycystic ovary syndrome.
  • Diagnosis:
    • High fasting blood glucose.
    • Glucose in urine.
    • Glucose tolerance test.
    • High insulin in type 2.
    • Acetone breath from ketoacidosis.
  • Treatment:
    • Type 1: insulin replacement.
    • Type 2: lifestyle changes (weight loss, exercise), oral drugs (increase insulin sensitivity or secretion), insulin if advanced.
    • Lipid-lowering drugs to reduce cardiovascular risk.

Insulin Excess (Hyperinsulinism)

  • Caused by insulinoma (beta cell tumor).
  • Leads to profound hypoglycemia and neurological symptoms.
  • Treatment includes glucose administration, glucagon, and tumor removal.

If you'd like, I can help you create a study guide or clarify any specific points!

Certainly! Here's a highly detailed, expanded bullet-point summary using the exact wording from the video, with added depth and clarity:

Pancreatic Endocrine Function

  • The pancreas has both digestive (exocrine) and endocrine functions; today’s focus is on the endocrine function.
  • The two main hormones secreted by the pancreas are insulin and glucagon, which regulate glucose, lipid, and protein metabolism to maintain homeostasis.
  • Other hormones secreted include amylin, somatostatin, and pancreatic polypeptides, but these play lesser roles in this chapter.
  • The pancreas is divided into two tissue groups:
    • Acini: secrete digestive enzymes.
    • Islets of Langerhans: contain endocrine cells.
  • Within the islets of Langerhans, there are three main cell types:
    • Alpha cells: secrete glucagon.
    • Beta cells: secrete insulin and amylin.
    • Delta cells: secrete somatostatin.
  • These hormones have paracrine effects, meaning they influence each other locally:
    • Insulin inhibits glucagon.
    • Amylin inhibits insulin.
    • Somatostatin inhibits both insulin and glucagon.
  • This interaction allows one hormone’s secretion to inhibit the others, enhancing the overall effect.

Insulin: Synthesis and Secretion

  • Insulin is secreted when there is an abundance of energy, mainly after meals when blood glucose is high.
  • Insulin’s main role is to package energy away by moving glucose, fats, and proteins from the bloodstream into cells for storage.
  • Insulin synthesis in beta cells:
    • Ribosomes produce preproinsulin.
    • Preproinsulin is cleaved in the endoplasmic reticulum to proinsulin (containing A, B, and C peptides).
    • The Golgi apparatus chops off the C-peptide, producing active insulin.
    • Insulin and C-peptide are packaged into secretory granules.
  • Measuring C-peptide levels can indicate endogenous insulin production, useful in diabetes management.
  • Insulin is not protein-bound in blood, so it is rapidly degraded (half-life ~6 minutes) by insulinase in the liver.

Insulin: Mechanism of Action

  • Insulin acts via a tyrosine kinase enzyme-linked receptor on the cell membrane.
  • Activation of this receptor phosphorylates intracellular enzymes, leading to:
    • Increased glucose uptake into muscle and adipose cells.
    • Increased permeability to amino acids, potassium, and phosphate ions.
    • Activation of metabolic enzymes for glycogen synthesis.
    • Increased transcription and translation of proteins over time.
  • The brain is insulin-independent for glucose uptake, ensuring constant glucose supply.
  • Muscle cells:
    • Increase glucose uptake and glycogen storage when insulin is present.
    • Cannot uptake glucose during fasting (no insulin), relying on fatty acid metabolism or stored glycogen.
    • During heavy exercise, muscle contraction increases glucose uptake via GLUT4 transporters, independent of insulin.
  • Liver cells:
    • Insulin promotes glucose uptake by increasing glucokinase activity, trapping glucose inside cells.
    • Insulin inhibits phosphorylase, preventing glycogen breakdown.
    • Insulin activates glycogen synthase, promoting glycogen formation.
    • During fasting (no insulin), these effects reverse, and the liver releases glucose via glycogenolysis and gluconeogenesis.

Insulin: Effects on Fat and Protein Metabolism

  • Fat metabolism:
    • Insulin promotes fat synthesis and storage by converting excess glucose into fatty acids in the liver.
    • Fatty acids are converted into triglycerides and transported to adipose tissue via lipoproteins.
    • Insulin activates lipoprotein lipase to break down triglycerides for adipose uptake.
    • Insulin inhibits hormone-sensitive lipase in adipose tissue, preventing fat breakdown.
    • Insulin promotes glucose uptake into fat cells, enhancing fat storage.
  • Without insulin:
    • Increased fat breakdown releases fatty acids and glycerol into the bloodstream.
    • The liver converts excess fatty acids into cholesterol and phospholipids, increasing lipoproteins and risk of atherosclerosis.
    • Fatty acids are converted into ketone bodies (acetoacetic acid), leading to ketoacidosis, which can cause coma and death.
    • Ketones cause a characteristic sweet breath odor.
  • Protein metabolism:
    • Insulin increases amino acid uptake into cells, promoting protein synthesis.
    • It inhibits protein catabolism and gluconeogenesis (conversion of amino acids to glucose).
    • Without insulin, protein breakdown increases, leading to muscle wasting, increased amino acids in blood, increased gluconeogenesis, and increased urea excretion.
    • This results in weakness and organ dysfunction.

Regulation of Insulin Secretion

  • The primary stimulus for insulin secretion is blood glucose concentration.
  • Glucose enters beta cells via GLUT2 transporters, is metabolized to produce ATP.
  • Increased ATP closes potassium channels, causing cell depolarization.
  • Depolarization opens calcium channels, allowing calcium influx.
  • Increased intracellular calcium triggers exocytosis of insulin.
  • Insulin secretion is biphasic:
    • First phase: rapid release of preformed insulin.
    • Second phase: sustained secretion as new insulin is synthesized.
  • Insulin secretion increases with rising glucose and plateaus at high glucose levels.
  • Other stimulators of insulin secretion (supplementary to glucose):
    • Amino acids (synergistic with glucose).
    • Gastrointestinal hormones (gastrin, cholecystokinin) — anticipatory increase during eating.
    • Glucagon (paradoxically increases insulin to prevent glucose roller coaster).
    • Growth hormone, cortisol, progesterone, estrogen (can antagonize insulin effects).
    • Parasympathetic nervous system (rest and digest) stimulates insulin secretion.
  • Sympathetic nervous system inhibits insulin secretion to maintain glucose availability during stress.

Glucagon: Actions and Regulation

  • Secreted by alpha cells when blood glucose falls.
  • Glucagon increases blood glucose by:
    • Activating adenyl cyclase → cAMP → protein kinase cascade.
    • Activating phosphorylase a, promoting glycogen breakdown in the liver.
    • Stimulating gluconeogenesis in the liver.
  • Glucagon promotes lipolysis in adipose tissue, increasing fatty acids for energy.
  • Other effects include enhancing heart strength, increasing blood flow, promoting bile secretion, and inhibiting gastric acid secretion.
  • Glucagon secretion is stimulated by:
    • Low blood glucose.
    • Amino acids.
    • Sympathetic stimulation (beta-adrenergic).

Somatostatin and Paracrine Regulation

  • Secreted by delta cells.
  • Somatostatin inhibits secretion of both insulin and glucagon, moderating hormone swings.
  • It decreases gastrointestinal motility and secretion, prolonging nutrient absorption.
  • Somatostatin from the hypothalamus also inhibits growth hormone release.

Blood Glucose Homeostasis

  • The liver acts as a buffer by storing glucose as glycogen when blood glucose is high and releasing glucose when low.
  • Insulin and glucagon provide feedback control to maintain blood glucose within normal limits.
  • Backup systems during severe hypoglycemia include epinephrine, growth hormone, and cortisol.
  • Both hypoglycemia and hyperglycemia have serious systemic effects:
    • Hypoglycemia affects brain function.
    • Hyperglycemia causes cellular dehydration, increased urination, ketoacidosis, atherosclerosis, hypertension, kidney disease, and blindness.

Diabetes Mellitus

  • Means "sweet urine" due to glucose in urine.
  • Type 1 diabetes:
    • Insulin-dependent; caused by autoimmune destruction of beta cells.
    • Usually juvenile onset (~14 years).
    • Characterized by insulin deficiency, hyperglycemia, fat and protein breakdown, ketosis, weight loss.
  • Type 2 diabetes:
    • Non-insulin dependent; caused by insulin resistance.
    • Usually adult onset, often associated with obesity.
    • Initially high insulin levels due to resistance; beta cells may become exhausted over time.
    • Similar complications as type 1.
  • Causes of insulin resistance include obesity, excessive glucocorticoids (Cushing’s syndrome, steroids), acromegaly, pregnancy (gestational diabetes), polycystic ovary syndrome.
  • Diagnosis:
    • High fasting blood glucose.
    • Glucose in urine.
    • Glucose tolerance test.
    • High insulin in type 2.
    • Acetone breath from ketoacidosis.
  • Treatment:
    • Type 1: insulin replacement.
    • Type 2: lifestyle changes (weight loss, exercise), oral drugs (increase insulin sensitivity or secretion), insulin if advanced.
    • Lipid-lowering drugs to reduce cardiovascular risk.

Insulin Excess (Hyperinsulinism)

  • Caused by insulinoma (beta cell tumor).
  • Leads to profound hypoglycemia and neurological symptoms.
  • Treatment includes glucose administration, glucagon, and tumor removal.

If you'd like, I can help you create a study guide or clarify any specific points!

Full transcript