//fpnotebook.com/
Glucose Metabolism
Aka: Glucose Metabolism
- Physiology
- Blood Glucose
- Released from hepatic stores between meals
- Derived from ingested carbohydrates
- Postprandial Glucose >20 fold over hepatic release
- Insulin
- General
- Insulin produced by pancreatic beta cells
- Insulin release stimulated by Blood Glucose
- Insulin response to Glucose is linear
- Insulin response is based on Glucose sensitivity
- Glucose sensitivity depends on Ambient Glucose
- Normal: Rapid Insulin release with a meal
- Fasting: Steeper rate of Insulin release
- Prolonged Hyperglycemia: Flattened response
- Phase 1 Insulin Release
- Duration: 10 minutes
- Suppresses hepatic Glucose release
- Phase 2 Insulin Release
- Duration: 2 hours
- Controls mealtime carbohydrates
- Basal Insulin Release
- Low continuous Insulin level
- Covers metabolic needs between meals
- Pathophysiology: Type II Diabetes Mellitus
- Loss of Glucose sensitivity (see above)
- Loss of phase 1 Insulin response
- Insufficient phase 2 Insulin response
- Insulin production by beta cell
- First: Insulin increases to overcome Glucose toxicity
- Results in beta-cell exhaustion (Glucose Toxicity)
- Initially reversible beta cell exhaustion
- Permanent later as amyloid replaces beta cells
- Insulin levels decrease as beta cells fail
- Beta-cell function reduced to <50% by DM diagnosis
- Impaired incretin action
- Incretins manage postprandial Glucose levels
- Incretin released from GI tract following meals
- Endogenous Incretin effects
- Increases Glucose dependent Insulin secretion
- Delays gastric emptying
- Decreases food intake (improves satiety)
- Progressive incretin reduced activity
- Glucagon-Like Peptide 1 (GLP-1) activity decreases
- Medications
- Increase Insulin sensitivity
- Metformin
- Thiazolidinediones
- Stimulate Insulin release from beta cells
- Meglitinides (act on phase 1 release)
- Sulfonylureas (act on phase 2 release)
- Replace Insulin
- See Insulin
- Increase incretin levels (GLP-1)
- Exenatide (Byetta)
- Sitagliptin (Januvia)