Insulin Sensitivity and insulin Resistance | Lecture Note - Edubirdie

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

2022
Views:

441

Pages:

3
Author:

Kyuwon J.

Insulin Sensitivity and insulin Resistance ● Tissues responds to given insulin concentrations ○ High levels in… ■ Livers ● Portal exposures ■ Muscles ● GLUT-4 uptake ■ Adipose tissues ● Insulin resistance ○ Reduce in biological response ■ Despite normal or high insulin ○ Could be seen early signs of hepatic insulin resistance ● Liver-specific insulin resistance ○ Paradox ■ Insulin fails ⇒cannot suppress gluconeogenesis ■ Insulin is still stimulated in lipogenesis ○ Hyperglycemia and fatty liver ■ NAFLD ○ Inflammation ■ TNF-a ■ IL-6 ○ Fatty acid free ○ Mitochondrial dysfunctions Insulin and Hepatic Glucose production ● HGP ○ Insulin suppression of HGP ■ Inhibition of PEPCK and G6Pase ■ Reduction of glycogen breakdown ■ Increase in glycolysis ○ Diabetes ■ Insulin signally fails ● FOXO1 pathway will also fail ■ Glucogenesis will still continue even with hyperinsulinemia ■ Liver becomes dominant source of hyperglycemia Clinical implications Fasting glucose => liver dysfunction instead of muscle uptakes Insulin clearance ● First pass hepatic extraction ○ 50% of insulin is cleared in liver ■ First pass ○ Systemic insulin levels ● Reduced clearance ○ Cirrhosis ○ NAFLD ○ Chronic inflammations ● Consequences ○ Peripheral hypersinulinemia ○ Downregulation on insulin receptors ○ Worsening insulin resistance Insulin + lipid metabolisms ● Adipose ○ Inhibition of hormone sensitivity of lipase ○ Suppression onf lipolysis ○ Decrease in fatty acids FFA ● Liver effect ○ Increase in triglycerides synthesis ○ Increase in VLDL productions

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