Insuline Metabolism | Lecture Note

University:
The University Of Western Ontario
Course:
Biology 2290F | Scientific Method in Biology
Academic year:

2022
Views:

178

Pages:

3
Author:

Kyuwon J.

Insulin’s integrated metabolic actions ● Insulin coordinates metabolism on skeletal muscles adipose tissues and liver ● Acts as central regulators ○ Green ■ Insulin stimulated processes ○ Red ■ Insulin inhibition processes Skeletal muscles ● Insulin effect ○ Uptakes of fatty acids increases ○ Glycogen synthesis increases ● Mechanisms ○ Insulin will bind to receptors on muscle cells ○ Activation of glycogen synthase ○ Increase in uptake+utilization on fatty acids ⇒ storage or oxidations ● Physiological meanings ○ Muscle acts s major glucose sink ■ Post prandialy ○ Shift muscle metabolism in anabolic, storage mode ○ Excessive glucose will be stored in form of glycogen ■ Does not remain in circulations Adipose tissues ● Insulin effects shown ○ Decrease in adipose lipolysis ○ Increase of fatty acid uptakes ● Mechanisms ○ Insulin inhibits hormone-sensitive lipase (HSL) ○ Suppression in breaking down triglycerides ■ Free fatty acids ■ Glycerol ● Decrease in release of FA + glycerol into the blood ● Increase in triglycerides in adipocytes ● Insulin preventing uncontrolled fat breakdowns ● Reduction of FA delivery towards liver ○ Defense on … ■ Ketogenesis ■ Hepatic insulin resistance ■ Lipotoxicity Reduction of FA and Glycerol Delivery on liver ● Since insulin suppresses adipose lipolysis ○ Decrease in free fatty acids going to liver ○ Decrease in glycerol substrate used for gluconeogenesis ● Important since liver relies on FA for energy ○ Glycerol for gluconeogenesis ● Insulin starves liver with substrates used for making glucose ● Indirectly lowers blood glucose levels Liver ● Integrates on direct insulin signaling ● Substrate availability AKT2 +SREBP1 pathway ● AKT2 ○ Insulin signaling kinase in hepatocytes ● Effects ○ Increase in glycogen synthesis ○ Increase in SREBP1 activations ● SREBP1 ○ Upregulation genes ■ Used for de novo lipogenesis (DNL) ■ Promotion of fatty acids ■ Triglyceride synthesis ● Liver stores glucose in form of glycogens ● Excess glucose will be converted to fat ○ DNL ○ Insulin promotes fatty liver if chronically elevated ○ Lipogenesis will remain active ■ Even in insulin resistance FOXO1 inhibitions ● Transcription factor which promotes ○ Gluconeogenesis ○ Expression of PEPCK and G6Pase ● Insulin effects ○ AKT phosphorylates FOXO1 ○ FOXO1 will be excluded from nucleus ⇒inactivations ○ Decrease in hepatic gluconeogenesis ● Insulin will directly shut down on glucose production with liver ● Main determinant on fasting down glucose levels