Endocrine Pancreas (Lopez) Flashcards by Daniel Aaron

major functions of the endocrine pancreas

regulate glucose, fatty acid, and amino acid metbaolism

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islets of Langerhans are innervated by what?

adrenergic, cholinergic, and peptidergic neruons

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what do B cells secrete of pancreas and location in islet

insulin and C peptide

located centrally

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what do alpha cells of pancreas secrete and location in islet

glucagon

located on periphery

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what do delta cells of the pancreas secrete and location in islet

somatostatin

located between alpha and beta cells

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physical aspect of delta cells

neuronal appearance, send dendrite-like processes to B cells and alpha cells

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what allows rapid communication between cells of islets

gap junctions

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blood supply of islets: venous from ___ carries ___ to other 2 cells

venous blood from B cells (with insulin) goes to alpha and delta cells and baths them. can
blood flows first to capillaries in center of islet and picks up insulin then to periphery where is acts on alpha cells to inhibit glucagon secretion

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beta cells negatively inhibit ___ cells to release __

a cells to release glucagon

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alpha cells can positively stimulate ___ cells to secrete __ with __

stimulate B cells to secrete insulin with glucagon acting as positive stimulator
(regulates too much glucose being in blood from glucagon)

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insulin synthesis

1) preprohormone made in ER with 4 peptides: signal sequence, A chain, B chain, C peptide
2) signal sequence cleaved and is now prohormone. Disulfide bridges from in ER (folded insulin)
3) packed into secretory vesicles in Golgi where proteases cleave off C peptide = insulin and C peptide in vesicles

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what is used to test B cell function in type 1 diabetes mellitus patients receiving insulin injections

C peptide (measures endogenous insulin)

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what receptor on the pancreatic B cell binds glucose

GLUT 2

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process of insulin release

1) glucose binds GLUT 2 on B cell in pancreas
2) GK phosphorylates to give Glucose-6-P
3) oxidation to ATP
4) shuts off K+ ATPase
5) depolarization of the cell and opening of calcium channels
6) calcium rushes in and causes stored vesicles of insulin to be released along with C peptide

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what drugs block the K+ ATPase on pancreatic B cell and this causes what? used for people with what

Sulfonylurea drugs (tolbutamide glyburide)
causes depolarization and release of insulin
help people with Type II DM

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insulin secretion is done in how many phases? explain

2 phases

initial is release of preformed insulin within 5-6 minutes
later stage is release of newly synthesized insulin, 20-30 minutes

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CCK and insulin. mechanism too

Gq, PLC—-> IP3—>Ca2+ = insulin release

—-> DAG—>PKC = insulin release

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which molecule has the same function and mechanism of insulin release as CCK?

Ach

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somatostatin mech on insulin

Gi which decreases cAMP and decreases insulin release

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Glucagon and ____ mechanism on insulin

GLP-1,

Gs—> increased cAMP and PKA and INCREASED insulin release

for insulin receptor tyrosine kinase autophos B subunits and itself and activates ___ which leasds to what

insulin receptor substrates (IRS) phos of enzymes

-either activates or inhibits these proteins to produce the metabolic actions of insulin

insulin secretion and clearance

pancreas creates and releases lots of insulin which is then taken up by the liver and 80% is excreted.
-much less insulin in circulation than pancreas originally makes

what transporter takes up glucose in the periphery and what uses this?

GLUT 4: liver, muscle, adipose tissue

what cells do not use GLUT 4 for glucose uptake

NS, kidney tubules, intestinal mucosa, RBC, and B cells of pancreas

insulin actions on the muscles - glucose uptake - glycogen syn - Hexokinase activity - gluconeogenesis - glycolysis - protein breakdown - protein synthesis

-increase glucose uptake w/ increased GLUT 4 transporter - increased glycogen synthesis - increased hexokinase which activates glycogen syn ``` -increased glycolysis: increased HK, PFK and PDH activity -decreased gluconeoenesis -increased protein synthesis -decreased protein breakdown ```

how does insulin inhibit gluconeogenesis in muscles

increase production of 2,6 bisphosphate which increases PFK activity and substrates directed away from formation of glucose

insulin effects on triglyceride and FA metabolism in adipose tissue - HSL - lipoprotein lipase - triglyceride formation - triglyceride breakdown - FA uptake - FA release - glucose uptake

- inhibits HSL (stops lipolysis) - increases lipoprotein lipase activity (breaksdown chylomicrons and triglycerides so they can be stored later as triglycerides in adipose tissue) - triglyceride formation increases - triglyceride breakdown decreases - FA uptake increases - FA release decreses - Glucose uptake increases - becomes a-glycerol-P + FA = triglyceride

insulin decreases what in the blood

ketoacids (not enough FA available) blood glucose amino acids FA

what enzyme in the liver is inactivated by insulin to prevent glycogenolysis

liver phosphorylase

insulin actions in the liver: __ glycogen synthesis ___ glucose release and ___ gluconeogenesis ___ glucose-6-phosphatase ___ glycolysis ___ acetyl coA, ___ FA synthesis ___ triglyceride storage and export (VLDLs) ___ protein syn, ___ protein degradation

increase glycogen syn decrease glucose release and decrease gluconeogen decrease glucose-6 phosphatase increase glycolysis increase acetyl coA and FA synthesis (sent to adipose tissue in VLDLs) increase TGs storage increase protein syn, decrease protein degradation

insulin actions in adipose tissue: ``` __ GLUT 4 ___glycolysis ___a-glycerol phosphate ___ acetyl coA, and FA syn ___ TGs ____ HSL ___ LPL ```

``` increase GLUT 4 increase glycolysis increase a-glycerol phosphate increase acetyl CoA and FA syn increase TGs decrease HSL increase LPL ```

insulin causes K+ to do what in the cells

be taken up by the cells and decrease K+ blood levels | -activates Na+/K+ ATPase

what inhibits insulin secretion

``` fasting decreased blood glucose exercise somatostatin a-adrenergic agonists (actiate Gi) Diazoxide ```

what stimulates insulin secretion

``` increased glucose, aa, FA, and ketoacids glucagon cortisol GIP ACh increased Blood K+ sulfonylurea drugs Obesity ```

diabetes mellitus type 1 __ conversion of FA to ketoacids and ___ ketoacid utilization by tissues

increases and decreases

3 causes for obesity-induced insulin resistance

1) decreased GLUT-4 uptake of glucose in response to insulin release 2) decreased ability of insulin to repress hepatic glucose production 3) inability of insulin to repress HSL and increase LPL

pathophysiology of DM type II

middle aged or older increased hepatic glucose production hyperglucagonemia (no insulin to down reg glucagon) not as prone to ketoacidosis (some insulin appears to protect from development)

why is hyperglucagonemia occuring in DM II

no insulin can get in the cells and down regulate glucagon release

how can DM II occur in non obese patients

decrease in insulin release by pancreas | varying degrees of insulin resistance can also occur

glucagon is a family of peptide that includes what

secretin and GIP

what stimulates glucagon release

``` decreased blood glucose ** increased aa (arginine and alanine) ``` Fasting CCK Ach B-adrenergic agonists free CAB

what inhibits glucagon release

insulin somatostatin increased FA increased ketoacid concentration

glucagon increases what in the blood

FA, glucose, and ketoacids

how does glucagon increase blood glucose (mech)

glucagon increases cAMP which activates PKA which decreases production of Fructose 2,6 BP---> increased gluconeogenesis -also increases glucogenolysis and inhibtis glycogen formation from glucose

glucagon __ lipolysis and inhibits ___ which shunts substrates toward gluconeogenesis

increases and inhibits FA syn

what are produced from FA

ketoacids

incretin hormones? what does it do to insulin and gastric emptying -glucagon secretion? responds to what?

GLP, GIP - secreted in response to GI glucose and fat - stimulate insulin secretion - inhibit glucagon secretion - slow gastric emptying

in insulin resistance: the ability of insulin to suppress ___ in adipose tissue and ___ secretion by alpha cells in the islet results in leads to __ in gluconeogenesis when defective

lipolysis, glucagon, increased gluconeogenesis