54 Pancreatic Hormone (Henry)

Question 1

List the cell types found in the pancreatic islets and their specific hormone secretions from each cell type.

Answer 1

Alpha Cells: glucagon and proglucagon
Beta Cells: insulin, C-peptide, proinsulin, islet amyloid polypeptide (IAPP), GABA
Delta Cells: somatostatin
Epsilon Cells: ghrelin
PP or F Cells: pancreatic polypeptide

Question 2

Identify the key biosynthetic steps, half-life, and regulators (stimulators, amplifiers, and inhibitors) of insulin secretion.

Answer 2

Peptide hormone, hydrophilic. Insulin gene translated to preproinsulin in ER, preproinsulin cleaved immediately. Proinsulin packaged into granules in Golgi. Proinsulin converted to insulin and C-peptide in secretory vesicles. Half-life is 3-5 mins, it circulates unbound. Release is pulsatile and periodic, regulated by the following pathways: neural, hormonal, and nutrient/ion regulation.

Glucose – most potent stim of release, increases intracellular ATP -> inhibits a K channel which depolarizes memb. Results in Ca influx and this is important in secretion of insulin containing vesicles.

Vagal Stimulation – acetylcholine activates M3 receptors and increases intracellular Ca.

Hormones – glucagon-like peptide (GLP1) amplifies insulin release.
Somatostatin can inhibit insulin release

Catecholamines – Beta adrenergic stim (epinephrine) can amplify secretion
Alpha-adrenergic stim can inhibit insulin release

Question 3

Describe the cellular events that take place during glucose and acetylcholine stimulated insulin secretion.

Answer 3

Glucose moves down conc. gradient into cell (likely thru glucose transporter 2), leads to increased ATP in cell. This inhibits K channel, memb depolarizes, and Ca flows in and is involved in insulin release.

Question 4

Define the cellular consequences that occur following activation of the insulin receptor.

Answer 4

Broadly, activates intracellular signaling pathways. Outcomes are mitogenic (cellular growth), and metabolic.

Question 5

Identify which tissues utilize glucose transporters for cellular uptake of glucose.

Answer 5

Glucose can’t move across cell memb. Energy dependent transport occurs in the kidney and gut. At all other sites, glucose moves down its concentration gradient. Insulin activates a receptor which activates or promotes channels (like GLUT4) to the memb and then glucose can move down the conc. gradient.

Glut 4 is on skeletal muscle and adipose tissue, insulin mediated uptake of glucose.
Glut 2 is on pancreatic B-cells, liver/kidney/gut, leads to insulin release.

Question 6

Describe the metabolic consequences of insulin in the liver, adipose tissue, and skeletal muscle.

Answer 6

Liver: Promotes anabolism: glycogen synth/storage. Inhibit glycogen breakdown, increase protein synth, and increase triglyceride synth.
Inhibits catabolism: inhibit glycogenolysis, inhibit ketogenesis, and inhibit gluconeogenesis.
Adipose tissue: Increase triglyceride storage by promoting free FA uptake, promote esterification of free Fas, and inhibit lipolysis.
Skeletal muscle: Increase protein synth by increasing AA uptake. Increases glycogen synth by increasing glucose uptake, increasing glycogen synthase activity, and inhibiting glycogen phosphorylase.

Question 7

List the regulators of glucagon secretion.

Answer 7

Glucagon has opposite effects of insulin, produced by alpha cells and in gut. Glucose inhibits glucagon secretion. Fatty acids suppress glucagon release. Catecholamines and GI hormones (like CCK, gastrin) promote glucagon release. Both para and symp stimulation promote glucagon release.

Question 8

Compare and contrast the impact of glucagon and insulin on the metabolic processes of gluconeogenesis, glycogenesis, glycogenolysis, glycolysis, and ketogenesis.

Answer 8

Insulin promotes energy storage while glucagon promotes energy mobilization

Question 9

Describe the physiological impact of insulin, glucose and glucagon administration on blood glucose levels.

Answer 9

Insulin decreases glucose in blood, glucagon rapidly increases glucose in blood

Question 10

Describe the physiological role of key pancreatic hormones (IAPP, pancreatic polypeptide, somatostatin, ghrelin) and predict the pharmacological impact of administering analogues or inhibitors of these agents to patients.

Answer 10

IAPP: produced by B cells. Packaged in same vesicles as insulin. Decreases glucagon secretion, inhibits GI motility, regulates appetite. Analogue can be used for type I and II diabetes.
Pancreatic Polypeptides: secreted by F or PP cells in pancreas. Regulated by vagus nerve and neuronal control. Regs exocrine function of pancreas, gallbladder contraction, gastric acid secretion, and GI motility.
Somatostatin: secreted by delta cells, secreted in response to same stimuli as insulin. Produced also in brain, periph neurons, endocrine cells of stomach/pancreas. Inhibits insulin secretion thru activation of SSTR-5
Ghrelin: Secreted by epsilon cells. Role not well understood. Produced also in heart, lung, kidney, IS, hypothal and pituitary. Shown to induce gastric emptying, gastric acid secretion, and increase appetite.

Glucagon Related Peptides (GLP)

Glucagon gene processed slightly differently can yield GLP1 and GLP2. GLP1 secreted in response to meal, is insulin secretion amplifier. GLP1 promotes production and secretion of insulin and somatostatin (is neg reg of insulin). GLP1 protects and promotes growth of B cells. DPP-4 can break down GLP1