The Endocrine Pancreas Flashcards
Insulin response to glucose
Biphasic; basic AAs will also stimulate this response
Incretin response to ingested glucose
Increased secretion from the GI tract leads to increased secretion of insulin; GLP-1 also suppresses glucagon secretion and is therefore more potent
- Requires glucose to produce strong stimulus
- GLP-1 and GIP are rapidly degraded by DPP4
Incretins in T2DM
Same amount produced; however, B-cells are less capable of responding
Mechanism of Insulin Secretion
Glucose enters the hepatocyte via GLUT-2 and is broken down by glucokinase producing ATP
=>Increased ATP binds to K+ channels depolarizing the cell and opening Ca2+ channels=>Release of insulin via exocytosis
Sulfonylureas
Bind to K+ channels promoting depolarization and the secretion of insulin from hepatocytes
Neural control of insulin release
Vagal stimulation => Increased
Exercise and stress => Decreased (via B2-adrenergic receptors)
Insulin Receptors
Involves the autophosphorylation of tyrosine kinases and the phosphorylation of IRS docking sites
=>PI-3 activation that leads to the mobilization of GLUT-4 to the plasma membrane
*Also capable of activating the MAP/Kinase pathway which
=>activation of Ras proteins and increasing transcription factors
Fate of the insulin hormone-receptor complex
Receptor is internalized, dephosphorylated, and degraded by endosomes
*Chronic exposure of insulin => increased internalization and degradation (down-regulation)
Control of Glucagon secretion
Hypoglycemia; low carb/protein ratio in meal
-Mediated in part by stimulation of B-adrenergic receptors
Characteristics of GLUT-2
Has a low affinity (high Kt) for glucose; therefore, entry to the hepatocyte is only permitted when glucose concentrations are high
*Much like how glucokinase has a high Km
Insulin effects in liver
- Increased expression of glucokinase
- Increased expression of glycogen synthase
- Prevents release of glucose
- Inhibits gluconeogenesis
- also inhibits protein metabolism peripherally
- Stimulates FA synthesis
Glucose Utilization in skeletal muscle
Is converted to either ATP or non-mobilizing glycogen
*Exercise can also stimulate the mobilization of more GLUT-4 transporters to the plasma membrane
Effects of insulin on Adipose
Moves GLUT-4 and activated LPL to the cell membrane to absorb glucose and FAs/glycerol respectively
-Inhibits lipolysis
Insulin effects on Ketogenesis
In the liver, insulin will decrease the flow of FAs to the liver and stimulate the formation of malonyl-CoA
-Inhibits the transport of FAs into the mitochondria where they would be oxidized
C-peptide
Product produced by the cleavage of insulin in the secretory granules of B-cells; proinsulin can also be produced in small amounts
Primary Source of glucose during a fast
The Liver: mostly glycogenolysis, some gluconeogenesis
Kidney: A small fraction of gluconeogenesis will occur in the kidney
Glucagon during a fast
(Liver)
- Increases expression of glucose-6-phosphatase
- Stimulates glycogenolysis/gluconeogenesis
- Promotes AA uptake
Cortisol during a fast
Promotes peripheral gluconeogenesis
*Glycogen only acts in the liver
GH during a fast
Levels will be increased in order to
- Inhibit glucose uptake in insulin-sensitive tissues
- Stimulate lipolysis and FA delivery to the liver for ketone production
Urea nitrogen during a fast
Increased due to increased breakdown of skeletal muscle proteins
Prolonged Fasting
- Drop in T3 => Drop in BMR
- Glucagon inhibits malonyl-CoA formation => ketongenesis
- Glucose, FFA, and insulin levels are stabilized
Sympathetic Signs of Hypoglycemia
Epinephrine release attempts to stimulate lipolysis, glycogenolysis, etc., but also causes palpitation, tachycardia, and sweating
Signs of neuroglycopenia
Lack of coordination, lack of concentration, dizziness, confusion, possible coma
Endocrine Response to Hypoglycemia
Release of GH (inhibits glucose uptake) and ACTH (promotes cortisol release)
