Diabetes Flashcards
metabolic regulation modes ?
#substrate availability #Allosteric #hormonal : Acute/ long-term adaptation
what goes on in the fasting state ?
it’s a catabolic period; energy is metabolized
how does glucagon signal ? how is the signal regulated ?
phosphodiesterases regulate the localization, duration, and amplitude of cyclic nucleotide signaling within subcellular domains. PDEs are therefore important regulators of signal transduction mediated by these second messenger molecules.
GPCR —> G protein activates adenylyl cyclase —> cAMP —> PKA —> phosphorylation kinase
the effet on isulin secretion on glucagon ?
insulin secretion inhibits glucagon secretion by alpha cells
effect of insulin on glycogen synthesis and breakdown ?
promotes the more active version of synthase and the less active veersion of phosphorylase
the effect of the rise in insulin/glucagon ratio on each of the regulatory steps of glycolysis ?
- Glucokinase stimulated by glucose,
results in increase in G6P.
2. G6P increases glycogen synthase
activity (allosteric), results in an
increase glycogen.
3. Increase in F2,6P2, stimulates
PFK-1.
4. F1,6P2 stimulates Pyruvate Kinase,
increasing pyruvate.
CPT ?
Mention some of the major regulators of fatty acid metabolism in the FED state
citrate from beta oxidation activates ACC (regulatory hormone of fatty acid synthesis)
role of AMPK and PKA ?
they stimulate beta oxidation and inhibit ACC (synthesis)
how does insulin reverse the effect of glucagon ?
it activates a phosphatase that reverses the glucagon0depndent phosphorylation of pyruvate kinase. (liver needs to metabolize glucose rather than synthesize it)
how do glucose transporters respond to insulin stimulation ?
when signal intensity of GLUT 4 was measured inside the cell and on the plasma membrane before and after insulin stimulation, there was a huge increase in plasma membrane transporters (recrution). —> indicates that GLUT 4 receptors are recruited from the cell’s interior in response to insulin stimulation. the complexity of the mechanism allows for exquisite control of GLUT-4
how are fats from the gut handled in the absorptive state ?
fats are transported from the gut via chylomicrons into the liver where TAGs are made and transported in VLDLs into adipose and muscle
glucose, insulin, glucagon correlation graph
how does liver adjust blood glucose in a fasted state ?
first by depleting glycogen stores and then gluconeogenesis
gluconeogenic substrate ?
amino acids (glutamate and alanine); lactate, glycerol
extended fasting ?
adipose –> beta oxidation –> glycerol sent to liver for gluconeogenesis–> FA sent to muscle and tissue and other body parts and liver for ketone body synthesis
muscle–> alot of protein breakdown –> alanine and glutamine sent to liver for gluconeogenesis
fatty acids, ketone bodies, glucose correlation chart
Diabetes types: elementary comparison
TYPE-1 no insulin secretion (dysfunctional beta cells)
MODY2 –> glucokinase molecule that is less sensitive or less responsive to rising levels of glucose. The beta cells in MODY 2 have a normal ability to make and secrete insulin, but do so only above an abnormally high threshold
dysfunction and death of beta cells in type-1 diabetes
elaborate on type-1 diabetes
Type 1 diabetes —\> autoimmune attack on beta cells of the pancreas —\> gradual depletion of beta cell degradation —\> symptoms appear abruptly; at this point pancreas fails to respond adequately to ingestion of glucose. #HYPERGLYCEMIA —\> due to high hepatic gluconeogenesis and lack of peripheral utilization by muscle and adipose that have INSULIN-DEPENDENT GLUT-4 #Ketosis —\> profuse fatty acid mobilization from adipose —\> ketone body synthesis —\> ketosis #acetyl coA from beta oxidation is used in ketogenesis and allosterically activates pyruvate carboxylase. #hypertriacylglycerolemia : the huge pool of FA’s trafficked into the liver isnt all oxidized or used for ketogenesis —\> trafficked out of the liver by VLVD’s and out of the gut by chylomicrons —\> BUT due to lack of lipoprotein insulin-dependent secretion, they remain in the blood causing hyperglycerolemia
insulin resistance instances ?
decreased uptake of glucose in liver and adipose
gluconeogenesis in liver
metabolic changes in T2D ?
Metabolic changes in T2D: #hyperglycemia: caused by increased hepatic production of glucose, combined with diminished peripheral us. ketosis is usually minimal or absent in patients with T2B because the presence of insulin, even in the presence of resistance, restrains hepatic ketogenesis. #Dyslipidemia: in the liver, FAs are converted to TAGs, which are packaged and secreted in VLDL. chylomicrons are synthesized from dietary lipids by the intestinal mucosal cells following a meal. because insulin-dependent, lipoprotein degradation catalyzed by lipoprotein lipase in adipose tissue is low in diabetics, the plasma chylomicron and VLDL levels are elevated, resulting in hypertriacylglycerolemia.
T2D pathology
Leptin Vs. Adiponectin
Leptin is a hormone secreted by adipose tissue that controls food intake and energy expenditure. Leptin resistance is associated with *obesity*.
