Week 8 Study Guide0

Week 8 Study Guide0 - Lectures#15-16: Tuesday, 2/23/2010...

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Lectures#15-16: Tuesday, 2/23/2010 and Thursday, 2/25/2010 Glucagon Effects Stimulators Inhibitors The Glucose Tolerance Test Pathologies Hyperglycemia Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Adipokines: Leptin, Adiponectin, Resistin Treatments and Pharmocological Intervention Metabolic Syndrome Hypoglycemia Glucagon Glucagon is secreted from the pancreatic alpha cells. Glucagon is antagonistic to insulin, and therefore, it is the ratio between insulin and glucagon levels that determines the metabolic direction, whether it is necessary to increase or decrease blood glucose levels. The Effects of Glucagon Glucagon’s primary role is to protect against hypoglycemia, and to this end, glucagon’s primary targets are the liver and adipose tissue. In adipocytes, glucagon promotes the activity of hormone sensitive lipase, which breaks down triglycerides into free fatty acids and glycerol. Thus, glucagon increases the availability of free fatty acids, which cells can use as energy sources via the β-oxidation pathway. The β-oxidation pathway converts free fatty acids into the ketone bodies, acetoacetic acid, β-hydroxybutyric acid, and acetone, which can be further metabolized through the Kreb’s cycle. Glucagon also promotes the conversion of glycerol to glucose via gluconeogenesis, by stimulating the activity of enzymes necessary for gluconeogenesis. In the liver, glucagon stimulates glycogenolysis, in addition to gluconeogenesis, thus increasing blood glucose levels. Glucagon stimulates glycogenolysis in the liver by binding to its Gs receptor. Hence, glucagon stimulation leads to increased adenylyl cyclase activity in the hepatocyte, which translates into increased cAMP levels, and increased PKA activity. In this pathway, PKA phosphorylates and activates glycogen phosphorylase kinase, which in turn, phosphorylates and activates glycogen phosphorylase, which phosphorylates glycogen and leads to the hydrolysis of one glucose-1-phosphate molecule from the glycogen chain. Then, hexokinase isomerizes glucose-1-phosphate molecule to glucose-6-phosphate, which is the first substrate of glycolysis. Refer to Figure 38 . Notably, the liver is unique in its role of supplying glucose for uptake by peripheral tissues. Although most tissues contain GLUT transporters, only the liver uses its GLUT2 transporter for both the uptake and release of glucose from and into the blood, whereas other cells, such as skeletal muscle cells, only use their GLUT transporters for glucose uptake. Recall that GLUT transporters can only transport free glucose, and not isomers of phosphorylated glucose. The hepatocytes are distinct from other cells in the body in that they contain a glucose-6-phosphatase, which cleaves the phosphate group from glucose-6-phosphate, yielding pure glucose, which can diffuse out of the hepatocyte and into the circulatory system
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under hypoglycemic conditions. Other cells, such as the skeletal muscle cells, do not contain this glucose-6-phosphatase, and as a result, they cannot produce pure glucose to transport out of the
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Week 8 Study Guide0 - Lectures#15-16: Tuesday, 2/23/2010...

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