Plasma Glucose Homeostasis

1. Plasma Glucose Homeostasis • Glucose metabolism • Hormonal Control • Disruptions of glucose homeostasis • Case Study

2. Homeostasis of Plasma Glucose Concentration • Normal physiological range: 65-100 mg/dl • Set point? • Plasma glucose concentration = glucose entering the plasma – glucose leaving the plasma • What are the mechanisms that regulate plasma glucose concentration? • What are the components of the negative feedback loop: • Glucose receptors? • Afferent pathway? • Integrator? • Efferent pathway(s)? • Effector organ(s)? Phases:*absorptive, *post-absorptive, and fasting

3. =sink Fig. 16.01 Lipoprotein Lipase Absorptive Phase Hepatic Portal System Once inside, glucose is converted to something else, thereby maintaining a concentration gradientfor facilitated diffusion ofglucose into cells.

4. Fig. 16.02 Special case: Muscle wasting of starvation Glucose Sparing Post-absorptive phase

5. Major Points • Absorptive phase lasts ~ 4 hours • During absorptive phase, energy needs provided by recently digested food • During absorptive phase, excess is converted to stored fuel • During post-absorptive phase, energy need met by release of stored fuels • Fasting defined as greater than 12 hours after previous meal (some say 24 hrs) • Fasting for several days has little effect on plasma glucose levels

6. The Issues • How do cells “know” which fuel to “burn?” • How do cells “know” when to synthesize glycogen or lipids and when to break down glycogen or lipid? • What is responsible for the transitions from the absorptive and post-absorptive states?

7. Islets of Langerhans Hepatic portal system Alpha cells secrete glucagon Beta cells secrete insulin Delta cells secrete somatostatin

8. Activates some enzymes, inactivates others Exercise via an undescribed mechanism Peptide hormone + GLUT-4 Which cell types have insulin receptors? T1DM =beta cells fail to produce adequate insulin (5%) T2DM = target cells “resistant” (less responsive) to insulin

9. =sink Fig. 16.01 =GLUT-4 Absorptive Phase Neurons don’t have insulin receptors, but do have Glucose transporters (not GLUT-4)

11. Fig. 16.04 Absorptive Phase Post-Absorptive Phase

12. Fig. 16.07 Identify sensors, afferent pathway,integrator,efferent pathway,effectors How is insulin secretion affected if plasma glucose is lower than set point?