176. Intermediary Metabolism Flashcards
In severe fasting state, ___ are mobilized from body protein stores and serve for ___
Amino acids
liver gluconeogenesis
Protein thats activity leads to glycogen synthesis in the liver and muscle after insulin binds to its receptor on the cell membrane
IRS-1
Produced in equimolar concentration from proinsulin and is released along w/ insulin
Better marker for endogenous insulin production than insulin given the longer half life
C-peptide
Lipids are either __ in peripheral tissue or converted to __ in liver during fasting state
Oxidation
Ketones
Stimulates insulin secretion from beta cells
- prevents excessive hyperglycemia
Glucagon
Main regulator of the rate of release of insulin and C-peptide from secretory vesicles
Plasma glucose levels
Cell depolarization activates ___ channels
Leads to a rise in cellular Ca2+
- augmented by Calcium release from the ER
Voltage-gated calcium
Insulin-dependent glucose transporter
Glucose uptake in muscle and fat cells trigger transposition of this transporter
GLUT-4
Sensitivity to __’s effect may be decreased in persons with chronic obesity
Inactivating mutations in the genes encoding __ or its receptor lead to massive obesity
Leptin
Main insulin dependent tissues are found in (3 things)
- (insulin-sensitive)
- stimulated in fed state
Muscle
Fat
Liver
Responsible for:
- glucose uptake in target tissues by transposition of GLUT-4
- Stimulation of glycogen synthesis and inhibition of glycogenolysis in the liver –> increased net uptake of glucose
- Induction of genes regulating storage of energy carriers in the form of glycogen and TG synthesis, mainly in the muscles and liver
- Induction of genes responsible for increased protein synthesis (anabolic effect)
- Decrease glucagon secretion
Insulin
Secreted by cells in the intestine (jejunum) in response to food intake
Facilitates insulin secretion from beta cells following oral intake
Agonists are used for the treatment of diabetes
GLP-1
ATP sensitive ___ channels on the cell membrane of beta cells react to the increase of ATP/ADP after glucose has entered the beta cells and become inhibited
- leads to cell depolarization
K+ (KATP channels)
Organ that can only use glucose for energy metabolism
Brain
List of energy resources from most to least:
Fat
Carbs
Protein
Secretes insulin
Beta-cells of islets of Langerhans
Inhibitory signals for __:
- somatostatin
- inflammatory cytokines
- NE
- Leptin
- IGF-1
Insulin
2 sources of glucose in hepatocytes from glycogenolysis and gluconeogenesis
Glycogen
Oxalate (leads to PEP from pyruvate)
Inhibitory signals for __:
- Glucose
- Insulin
- Somatostatin
- Ketones
- Free fatty acids
- GLP-1
Glucagon
Secreted by alpha cells in the islets of Langerhans
Counteracts insulin in respect to glucose uptake and metabolism
Glucagon
Glucose transporter in fat and muscle
GLUT4
Secreted by adipose tissue proportional to its mass
Induces satiety, increases energy expenditure
Currently being explored for treatment of obesity and/or diabetes
Leptin
Stimulatory signals for __:
- Amino acids
- ACh
- EPI
- NE
- GIP
- CCK
Glucagon
Activates glycogen breakdown after cAMP acts on it
Blocked by insulin
PKA
Displays a diurnal variation in plasma levels
Relates to conditioning to common times when one eats
Ghrelin
Rise in intracellular calcium triggers fusion of __ and __ containing vesicles with the cell membrane and exocytosis of these prestored proteins
Insulin and C-peptide
Released mainly by cells in the stomach and intestinal wall
Levels ride during fasting
- induce hunger and promote energy conservation
Ghrelin
GLUT4 responds to __ action after it is phosphorylated by the Insulin/IGF-1 receptors
Translocates GLUT4 to cell membrane to let glucose enter the cell
Cbl
Plasma glucose is sensed by beta cells via free entry of glucose into beta cells through what transporter?
Insulin-independent
GLUT-2
Enhances glucose stimulated insulin
Inhibits glucagon secretion
Delays gastric emptying
Induces satiety
Acts through a G-coupled cell membrane receptor
GLP-1
After glucose enters the beta cells via GLUT-2, it causes oxidative metabolism of itself leading to an increase in the what?
ATP/ADP ratio
Peptide hormone with a relatively short half-life that binds to tyrosine kinase receptors to initiate an intracellular signaling cascade
Insulin
Deactivated by phosphorylated PKB
Can no longer inactivate glycogen synthesis
GSK3
Acts on a GPCR that leads to activation of PKA to inactivate glycogen synthase
Also helps leads to glycogen breakdown
Glucagon
Stimulatory signals for __:
- Glucose
- GLP-1
- Glucagon
- Amino acids
- Fatty acids
- ketones
- ACh
- VIP
- EPI
Insulin
Peptidase that degrades GLP-1
Target of inhibition in diabetic medications
DPP-4
