1-21 DSA Pancreatic Function and Carbohydrate Metabolism Flashcards
What are the 4 secretory cells of the pancreatic islets of Langerhans?
alpha
beta
delta
F (cells)
What is the primary secretion of alpha cells of the pancreatic islets of Langerhans?
Glucagon
What is the primary secretion of beta cells of the pancreatic islets of Langerhans?
Insulin
Proinsulin
C-peptide
Amylin
What is the primary secretion of delta cells of the pancreatic islets of Langerhans?
Somatostatin
What is the primary secretion of F cells of the pancreatic islets of Langerhans?
pancreatic polypeptide
F cells are AKA pancreatic polypeptide cells
How can humoral factors impact islet cell secretion?
Beta cells tend to be in the middle of the islets, with blood supply to the edges (that contain more alpha or delta cells) that is ‘downstream’ of beta cells.
Insulin will act in a paracrine manner on ‘downstream’ cells to modulate their release of hormones - insulin slightly inhibits release of glucagon. Somatostatin inhibits insulin and glucagon.
How can cell-to-cell communication methods impact islet cell secretion? What hormones are affected?
Islet cells connected by tight and gap junctions
- gap jxns allow communication
- important for regulation of insulin and glucagon secretion
How can neural communication methods impact islet cell secretion?
Happens via ANS
Cholinergic - Para
- increases insulin
Adrenergic - Sym
- goes both ways
- beta: stimulatory
- alpha: inhibitory
What metabolic processes predominate in the fasting stage?
(Keep in mind that insulin integrates body fuel metabolism in fasting and feeding.)
Fasting:
- beta cells release less insulin
- lipids freed from adipocytes
- AAs are freed from body protein stores
Lipids & AAs provide fuel for oxygenation
- also serve as precursors for hepatic ketogenesis and gluconeogenesis
What metabolic processes predominate in the feeding stage?
Increased insulin reduces:
- mobilization of endogenous fuel stores
Increased insulin increases:
- carb, lipid, AA uptake by insulin sensitive target tissues
Insulin directs tissue to replenish fuel reserves used during fasting.
- AKA, a metabolic summary of Christmas break
What substances/variables can trigger insulin release?
Glucagon
Depolarizing islet cell membrane
Beta cells taking up:
glucose
galactose
mannose
Weak stimulation from:
- some AAs - arg and leu
- small keto acids (alpha ketoisocaproate)
- ketohexoses (fructoses)
Hormones:
- CCK
- Glucagon
What is the 7 step process in which glucose triggers insulin release?
- Glucose enters the β cell through the GLUT2 glucose transporter by facilitated diffusion. Amino acids enter through a different set of transporters.
- In the presence of glucokinase (the rate-limiting enzyme in glycolysis), the entering glucose undergoes glycolysis and raises [ATP]i by phosphorylating ADP. Some amino acids also enter the citric acid cycle and produce similar changes in [ATP]i and [ADP]i. In both cases, the NADH/NAD+ ratio also would increase.
- The increased [ATP]i, the increased [ATP]i/[ADP]i ratio, or the elevated [NADH]i/[NAD+]i ratio causes KATP channels to close.
- Reducing the K+ conductance of the cell membrane causes the β cell to depolarize (i.e., the membrane potential is less negative).
- This depolarization activates voltage-gated Ca2+ channels.
- The increased Ca2+ permeability leads to increased Ca2+ influx and increased intracellular free Ca2+. This rise in [Ca2+]i additionally triggers Ca2+-induced Ca2+ release.
- The increased [Ca2+]i, perhaps by activation of a Ca2+-calmodulin phosphorylation cascade, ultimately leads to insulin release.
What is the effect of alpha-adrenergic stimulation on on insulin secretion?
Inhibits it
What is the effect of beta-adrenergic stimulation on on insulin secretion?
Stimulates it
- i.e. isoproterenol
What is the effect of cholinergic stimulation on on insulin secretion?
Stimulates it
- ACh from CN X
What is the effect of signalling from the celiac nerves on insulin secretion?
Because the postsynaptic sympathetic neurons of the pancreas release norepinephrine, which stimulates α more than β adrenoceptors, sympathetic stimulation through the celiac nerves inhibits insulin secretion.
What is the specific effect of insulin on the metabolic processes of the liver?
Insulin stimulates formation of glycogen:
- activates glucokinase and glycogen synthase
- attenuates glycogen phosphorylase, which normally breaks down glycogen
- inhibits glucose-6-phosphatase
Insulin promotes conversion of glucose into pyruvate
- also attenuates use of pyruvate and other 3-C molecules for gluconeogenesis
Insulin activates: glucokinase phosphofructokinase pyruvate kinase pyruvate dehydrogenase hexose monophosphate shunt acetyl CoA carboxylase fatty acid synthase apoprotein synthesis for VLDLs
Insulin inhibits:
- gluconeogenesis
- G-6-Pase
- glycogen phosphorylase
What is the specific effect of insulin on the metabolic processes of adipose tissue?
Insulin promotes fat storage
- inhibits oxidation of FAs
Insulin deactivates:
carnitine acyltransferase I - prevents transport of FAs for oxidation
Insulin activates:
malonyl CoA synthesis - inhibits FA transport to mitochondria
fatty acid synthase - generates FAs
creation of triglycerides
What is the specific effect of insulin on the metabolic processes of muscle tissue?
- Insulin potentiates uptake of glucose via GLUT4
- increases Vmax transport of glucose into mm tissue - Insulin activates hexokinase and glycogen synthase
- Insulin increases phosphofructokinase and pyruvate dehydrogenase
- Insulin stimulates protein synthesis
- inhibits degradation/proteolysis
What is the effect of insulin and glucagon on glycogen synthesis?
Insulin: stimulates
Glucagon: inhibits
What is the effect of insulin and glucagon on glycogenolysis?
Insulin: inhibits
Glucagon: stimulates
What is the effect of insulin and glucagon on glycolysis?
Insulin: stimulates.
Glucagon: inhibit
What is the effect of insulin and glucagon on gluconeogenesis?
Insulin: inhibits
Glucagon: stimulates
What is the effect of insulin and glucagon on lipogenesis?
Insulin: inhibits
Glucagon: stimulates
What is the effect of insulin and glucagon on lipolysis?
Insulin: inhibits
Glucagon: stimulates
What is the effect of insulin and glucagon on protein degradation?
Insulin: inhibits
Glucagon: stimulates
What is the effect of insulin and glucagon on protein synthesis?
Insulin: stimulates
Glucagon: inhibits
What are the main effects of glucagon on the liver?
Glucagon is particularly important in stimulating glycogenolysis, gluconeogenesis, and ketogenesis.
