Week 1 - Hormonal Regulation of Carbohydrate Metabolism Flashcards
What are the acute manifestations of HYPOglycemia?
Palpitations, tachycardia, diaphoresis, anxiety, weakness, hunger, nausea
What are the chronic manifestations of HYPOglycemia?
hypothermia, confusion, hallucinations, seizure, coma
What are the acute manifestations of HYPERglycemia?
polydipsia, polyphagia, altered vision, weight loss, mild dehydration
What are the chronic manifestations of HYPERglycemia?
cardiac arrhythmias, coma
What portion of the pancreas is endocrine?
The islets; make up 1-3% of pancreas
What do beta-cells secrete?
insulin & IAPP (Islet Amyloid Polypeptide)
What is the function of IAPP?
Slows gastric emptying and inhibits glucagon secretion
What portion of islet endocrine cells are beta cells?
~60%
What do alpha-cells secrete?
glucagon
What do delta-cells secrete?
somatostatin
What is the function of somatostatin?
inhibits both insulin & glucagon
Aside from alpha, beta, and delta cells, what are the other type of pancreatic islet cells?
- what do they secrete?
PP cells
- secrete pancreatic polypeptide
What is the function of PP (pancreatic polypeptide)?
reduces appetite and food intake
What is the parasympathetic innervation to the pancreatic islet?
- what neurotransmitter?
- what is its effect?
Vagus nerve
- ACh
- increases insulin release
What is the sympathetic innervation of pancreatic islets?
- what neurotransmitter?
- what is its effect?
Post ganglionic fibers of celiac ganglion
- NE
- inhibits insulin secretion
What is the precursor to insulin in the synthesis pathway?
- where is it synthesized?
Proinsulin (A- & B-chains; C-peptide)
- RER of beta-cell
What stimulates insulin secretion?
- glucose, Arg/Lys, FFA
- GIP, GLP-1, glucagon
- ACh
What inhibits insulin secretion?
- NE/Epi
- Somatostatin
- Prolonged glc&FFA
How does glc stimulate insulin secretion?
Glc enters beta-cells via GLUT-2
- phosphorylated to Glc-6-PO4
- glycolysis –> makes ATP
- closes ATP-sensitive K+ channels
- generates AP (depolarization)
- Ca++ channels open (Ca++ flows into cell)
- exocytosis of insulin granules
What are the major target tissues for insulin?
Muscle, fat, liver
What organs have GLUT-2?
Liver & pancreatic beta-cells
What is the action of insulin on fat & muscle cells?
- insulin binds receptor
- PI3K signalling pathway
- stimulates translocation of GLUT-4 vesicles
- GLUT-4 expressed on cell surface
- glucose enters cell
What are the acute effects of insulin on individual target tissues?
Fat - glc gets stored as fat (lipogenesis)
Muscle - glc used as energy or stored (as glycogen or protein)
Liver - increases glycogen synthesis; inhibits gluconeogenesis & glyogenolysis;
Specifically how does insulin cause increased fatty acid and triglyceride synthesis?
Stimulate lipoprotein lipase (breaks down lipoproteins to FFAs –> can enter adipocyte)
Stimulates FA synthesis from glc
Inhibits hormone-sensitive triglyceride lipase - inhibits triglyceride breakdown in adipocytes
The insulin receptor is in what class of receptor types?
Tyrosine kinase
What is included as part of the proglucagon molecule?
GRPP, Glucagon, IP-1, GLP-1, IP-2, GLP-2
What are enteroendocrine cells?
Specialized endocrine cells in GI tract and pancreas
- respond to stimuli to produce GI hormones/peptides
- initiate digestive actions & detect toxins
Name some specific enteroendocrine cells in the intestine and state their function.
K cells - secrete GIP
L cells - secrete GLP-1 & GLP-2
Enterochromaffin cells - secrete serotonin
What is GIP?
Gastric Inhibitory Peptide (an incretin)
What is GLP-1?
Glucagon-like peptide-1 (an incretin)
What enteroendocrine cells are found in the stomach?
- what is their function?
G cells - secrete gastrin
Enterochromaffin-like cells - secrete histamine
What enteroendocrine cells are found in the pancreas?
alpha-cells, beta-cells, delta-cells, PP cells
What is ghrelin?
- where is it produced?
- what causes it to be released?
- where does it act?
- what is its effect?
“hunger hormone” “Growth Hormone RELease-INducing”
- produced in GI tract (mainly stomach & duodenum)
- in response to empty stomach
- acts on hypothalamus
- increases feeling of hunger, increases gastric acid secretion & GI motility, decreases insulin secretion
What is the major site of glucagon action?
- what are glucagon’s effects there?
Liver
- increase glycogenolysis
- increase gluconeogenesis
What stimulates glucagon release?
- hypoglycemia
- amino acids
- GIP, CCK
- ACh, NE
What inhibits glucagon release?
- insulin, somatostatin
- GLP-1
How does the ANS directly affect metabolism regulation in the liver?
Sympathetic: stimulates hepatic glc output
Parasympathetic (vagus): stimulates hepatic glc uptake
What are some counterregulatory horomones to insulin?
GH, Cortisol, Epi
How does cortisol affect glc homeostasis?
- cortisol is released in response to low glc
- stimulates gluconeogenesis
- decreases translocation of GLUT-4
- INCREASES glycogen synthesis
