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*GIGU I > 17. Endocrine Pancreas > Flashcards

17. Endocrine Pancreas Flashcards

1
Q

The endocrine cells of the pancreas secrete 3 separate hormones

Beta cells secrete ____

Alpha cells secrete ____

Delta cells secrete ______

A

Insulin (and C peptide)

Glucagon

Somatostatin

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2
Q

The beta, alpha, and delta cells of the pancreas are organized into clusters called ____

A

Islets (of langerhans)

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3
Q

Which cells of the pancreas are neuronal in appearance and send dendrite like processes to beta cells?

A

Delta cells

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4
Q

Most ____ cells of the pancreas are centrally located, while most _____ are peripherally located

A

Beta; alpha

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5
Q

How do individual islets in the endocrine pancreas communicate with each other?

A

Via gap junctions - rapid cell-cell communication

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6
Q

Describe blood supply to the endocrine pancreas - which cells receive blood first?

A

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]

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7
Q

What is the major stimulating factor for insulin secretion?

A

Glucose

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8
Q

Insulin is a _____ hormone made up of 2 chains linked by _____ bridges

A

Peptide; disulfide

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9
Q

_______ = signal peptide with A and B chains with connecting C peptide - NO disulfide bonds

A

Preproinsulin

[preproinsulin —> proinsulin —> Insulin + C peptide]

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10
Q

______= no signal peptide because C peptide still attached to insulin; packaged into secretory granules, proteases can cleave it

A

Proinsulin

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11
Q

Once synthesized, insulin and cleaved C peptide are packaged together in ______

A

Secretory vesicles

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12
Q

What compound can be used as a marker of endogenous insulin secretion?

A

C peptide

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13
Q

Steps for insulin release:

  1. Glucose enters cell via ______
  2. Glucose is phosphorylated by a ________
  3. G6P is oxidized, promoting ___ generation
  4. ATP closes the inward rectifying ____ channel
  5. Plasma membrane is depolarized
  6. Activation of voltage gated ___ channels leading to its entry into the cell
  7. Mobilization of insulin is initiated
A 
GLUT2
Glucokinase
ATP
K
Ca
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14
Q

Rises in ATP have what effect on K channels in beta cells?

A

Rises in ATP close the K channels

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15
Q

The sulfonurea receptor associated with ATP-dependent K channels increase insulin secretion. what effect does this have on membrane depolarization?

A

Causes membrane depolarization to occur more easily d/t increased Ca entry - so this can be targeted and used for tx of T2DM

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16
Q

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 ____

A

Urine

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17
Q

Describe the biphasic release of insulin and how this is affected in diabetics

A

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

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18
Q

Besides blood glucose levels, what are some other modulators of insulin secretion?

A

Activating:
GI peptides
Glucagon
ACh

Inhibitory:
Somatostatin

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19
Q

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

A

Autophosphorylates; mTORC1; SREBP1c

20
Q

Glucose uptake occurs through _______, once vescicles containing this transporter to the membrane

A

GLUT4

21
Q

Activation of _______ results in GLUT4 transloaction to the plasma membrane INDEPENDENT of insulin

A

AMP-kinase

[active in times of low energy]

22
Q

Actions of insulin on skeletal muscle

A

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

23
Q

Action of insulin on liver

A

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

24
Q

Insulin actions on adipose tissue

A

Increased glucose uptake via GLUT4

Increased glycolysis

Decreased lipolysis

Promotes uptake of fatty acids

25
Q

What effect does insulin have on K+ uptake into cells?

A

Increases K uptake into cells (thus decreasing blood levels of K)

26
Q

Which of the following increases insulin secretion?

A. Fasting
B. Somatostatin
C. Cortisol
D. Exercise
E. Diazoxide
A

C. Cortisol

27
Q

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 ______

A

Beta

Ketoacids

DKA (diabetic ketoacidosis)

28
Q

What effect does T1DM have on blood potassium levels?

A

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]

29
Q

What effect does T1DM have on diuresis?

A

Causes osmotic diuresis and glucosuria

[also polydipsia d/t increased polyuria]

30
Q

Which type makes up 95% of DM cases?

A

T2DM

31
Q

T1DM is insulin deficiency. What causes T2DM?

A

Insulin resistance — progressive exhaustion of beta cells d/t environmental and genetic factors

32
Q

The progression of insulin resistance in t2DM begins as reactive ______ followed by relative _____

A

Hyperinsulinemia; hypoinsulinemia

33
Q

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

A

GLUT4

Hepatic

Adipose

34
Q

T/F: those with T2DM are more prone to ketoacidosis than T1DM patients

A

False; other way around

35
Q

Treatment options for T2DM

A

Caloric restriction, weight reduction, PE

Insulin secretagogues - sulfonurea drugs, incretin analogues

Insulin sensitizers

Bariatric surgery

Alpha-glucosidase inhibitors, amylin analogues

36
Q

What is the incretin effect that insulin has on skeletal muscle?

A

Oral intake elicits better response than injection

37
Q

What are some incretin hormones? What effects do they have on insulin secretion, glucagon secretion, and gastric emptying?

A

Intestine derived hormones = GLP-1, GIP

Stimulate insulin secretion, inhibit glugcagon secretion, slow gastric emptying

38
Q

Will type 2 diabetics show a normal, enhanced, or reduced incretin effect?

A

Reduced

39
Q

______ is a hormone in the same peptide family as secretin and GIP, stored in dense granules of alpha cells

A

Glucagon

40
Q

What is the primary major stimulus for secretion of glucagon?

A

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]

41
Q

What effect does insulin have on glucagon production and secretion?

A

Inhibits

42
Q

Which of the following stimulates glucagon secretion?

A. Insulin
B. Somatostatin
C. Fatty acids
D. Ketoacids
E. None of the above
A

E. None of the above

43
Q

The major actions of glucagon are on what organ?

A

Liver

44
Q

What effect does glucagon have on the liver in terms of glucose formation, gluconeogenesis, glycogenolysis, and glycogen synthesis?

A

Increases glucose formation via gluconeogenesis and glycogenolysis

Inhibits glycogen synthesis

45
Q

What effect does glucagon have on lipolysis in adipose and skeletal muscle?

A

Stimulates lipolysis

[which produces ketoacids from fatty acids]

*GIGU I (67 decks)

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