17. Endocrine Pancreas Flashcards
The endocrine cells of the pancreas secrete 3 separate hormones
Beta cells secrete ____
Alpha cells secrete ____
Delta cells secrete ______
Insulin (and C peptide)
Glucagon
Somatostatin
The beta, alpha, and delta cells of the pancreas are organized into clusters called ____
Islets (of langerhans)
Which cells of the pancreas are neuronal in appearance and send dendrite like processes to beta cells?
Delta cells
Most ____ cells of the pancreas are centrally located, while most _____ are peripherally located
Beta; alpha
How do individual islets in the endocrine pancreas communicate with each other?
Via gap junctions - rapid cell-cell communication
Describe blood supply to the endocrine pancreas - which cells receive blood first?
Venous blood first flows to center for insulin; venous blood from beta cells carries insulin to alpha and delta cells
[flows through periphery, insulin rich blood inhibits glucagon release from alpha cells]
What is the major stimulating factor for insulin secretion?
Glucose
Insulin is a _____ hormone made up of 2 chains linked by _____ bridges
Peptide; disulfide
_______ = signal peptide with A and B chains with connecting C peptide - NO disulfide bonds
Preproinsulin
[preproinsulin —> proinsulin —> Insulin + C peptide]
______= no signal peptide because C peptide still attached to insulin; packaged into secretory granules, proteases can cleave it
Proinsulin
Once synthesized, insulin and cleaved C peptide are packaged together in ______
Secretory vesicles
What compound can be used as a marker of endogenous insulin secretion?
C peptide
Steps for insulin release:
- Glucose enters cell via ______
- Glucose is phosphorylated by a ________
- G6P is oxidized, promoting ___ generation
- ATP closes the inward rectifying ____ channel
- Plasma membrane is depolarized
- Activation of voltage gated ___ channels leading to its entry into the cell
- Mobilization of insulin is initiated
GLUT2 Glucokinase ATP K Ca
Rises in ATP have what effect on K channels in beta cells?
Rises in ATP close the K channels
The sulfonurea receptor associated with ATP-dependent K channels increase insulin secretion. what effect does this have on membrane depolarization?
Causes membrane depolarization to occur more easily d/t increased Ca entry - so this can be targeted and used for tx of T2DM
C peptide secretion is used as a tool to measure function of beta cells and endogenous insulin secretion. C peptide is typically secreted in the ____
Urine
Describe the biphasic release of insulin and how this is affected in diabetics
When plasma glucose increases:
Phase 1 = initial spike in insulin secretion
Phase 2 = gradual sustained rise in insulin secretion
In diabetes — phase 1 is the first phase lost
Besides blood glucose levels, what are some other modulators of insulin secretion?
Activating:
GI peptides
Glucagon
ACh
Inhibitory:
Somatostatin
Once insulin binds its receptor, it ________ itself and other proteins. The entire complex is internalized by target cell, leading to anabolic growth effects and metabolic effects, eventually leading to activation of ______ and ______ which have a negative feedback effect on the receptor itself
Autophosphorylates; mTORC1; SREBP1c
Glucose uptake occurs through _______, once vescicles containing this transporter to the membrane
GLUT4
Activation of _______ results in GLUT4 transloaction to the plasma membrane INDEPENDENT of insulin
AMP-kinase
[active in times of low energy]
Actions of insulin on skeletal muscle
Increased glucose uptake via GLUT4
Increased glycogen synthesis via activity of hexokinase and glycogen synthase
Increased glycolysis and CHO oxidation via activity of hexokinase, PFK, PDH
Increased protein synthesis
Decreased protein breakdown
Action of insulin on liver
Promotes glycogen synthesis via glucokinase and glycogen synthase
Increases glycolysis and CHO oxidation via glucokinase, PFK, PK
Decreases gluconeogenesis
increases hexose monophosphate shunt (protein anabolism)
Increases pyruvate oxidation
Increases lipid sotrage and decreases lipid oxidation
Increases protein synthesis and decreases protein breakdown
Insulin actions on adipose tissue
Increased glucose uptake via GLUT4
Increased glycolysis
Decreased lipolysis
Promotes uptake of fatty acids
What effect does insulin have on K+ uptake into cells?
Increases K uptake into cells (thus decreasing blood levels of K)
Which of the following increases insulin secretion?
A. Fasting B. Somatostatin C. Cortisol D. Exercise E. Diazoxide
C. Cortisol
Type 1 diabetes is often d/t autoimmune destruction of ___ cells, leading to inadequate insulin secretion
Results in increased BG, fatty acids, _______, amino acids
Decreased utilization of ketoacids results in ______
Beta
Ketoacids
DKA (diabetic ketoacidosis)
What effect does T1DM have on blood potassium levels?
Increases shift of K+ out of cells —> hyperkalemia
[intracellular concentration of K is low, lack of insulin effect on Na/K ATPase, total K levels usually low d/t polyuria and dehydration]
What effect does T1DM have on diuresis?
Causes osmotic diuresis and glucosuria
[also polydipsia d/t increased polyuria]
Which type makes up 95% of DM cases?
T2DM
T1DM is insulin deficiency. What causes T2DM?
Insulin resistance — progressive exhaustion of beta cells d/t environmental and genetic factors
The progression of insulin resistance in t2DM begins as reactive ______ followed by relative _____
Hyperinsulinemia; hypoinsulinemia
Obesity induced insulin resistance begins with decreased ____ uptake of glucose in response to insulin (classical skeletal muscle impairment)
Decreased ability of insulin to repress _____ glucose production (may be earliest response)
Inability of insulin to repress _____ tissue uptake via LPL and lipolysis via HSL
GLUT4
Hepatic
Adipose
T/F: those with T2DM are more prone to ketoacidosis than T1DM patients
False; other way around
Treatment options for T2DM
Caloric restriction, weight reduction, PE
Insulin secretagogues - sulfonurea drugs, incretin analogues
Insulin sensitizers
Bariatric surgery
Alpha-glucosidase inhibitors, amylin analogues
What is the incretin effect that insulin has on skeletal muscle?
Oral intake elicits better response than injection
What are some incretin hormones? What effects do they have on insulin secretion, glucagon secretion, and gastric emptying?
Intestine derived hormones = GLP-1, GIP
Stimulate insulin secretion, inhibit glugcagon secretion, slow gastric emptying
Will type 2 diabetics show a normal, enhanced, or reduced incretin effect?
Reduced
______ is a hormone in the same peptide family as secretin and GIP, stored in dense granules of alpha cells
Glucagon
What is the primary major stimulus for secretion of glucagon?
Major stimulus = Decreased blood glucose via GLUT, K(ATP), and VDCC in alpha cell membrane (similar to beta cells)
[may also be stimulated by increased aa like arginine and alanine, fasting, CCK, beta adrenergic agonists, ACh]
What effect does insulin have on glucagon production and secretion?
Inhibits
Which of the following stimulates glucagon secretion?
A. Insulin B. Somatostatin C. Fatty acids D. Ketoacids E. None of the above
E. None of the above
The major actions of glucagon are on what organ?
Liver
What effect does glucagon have on the liver in terms of glucose formation, gluconeogenesis, glycogenolysis, and glycogen synthesis?
Increases glucose formation via gluconeogenesis and glycogenolysis
Inhibits glycogen synthesis
What effect does glucagon have on lipolysis in adipose and skeletal muscle?
Stimulates lipolysis
[which produces ketoacids from fatty acids]
