PERTURBATION OF METABOLISM IN INSULIN DIABETES (Q1 &2) Contents DESCRIBE THE EFFECT OF INSULIN DEFICIENCY ON THE REGULATION OF THE PATHWAYS OF GLYCOLYSIS AND GLUCONEOGENESIS AND THE UPTAKE OF GLUCOSE INTO MUSCLE AND ADIPOSE TISSUE ......................................... 1 EXPLAIN HOW THE LACK OF INSULIN IN DKA LEADS TO OVERPRODUCTION OF GLUCAGON WITH STIMULATION OF GLUCONEOGENESIS AND LIPOLYSIS .......................................................................................................................... 2 REFERENCES.............................................................................................................................................................. 3 DESCRIBE THE EFFECT OF INSULIN DEFICIENCY ON THE REGULATION OF THE PATHWAYS OF GLYCOLYSIS AND GLUCONEOGENESIS AND THE UPTAKE OF GLUCOSE INTO MUSCLE AND ADIPOSE TISSUE The presence of insulin (in healthy individual) after eating a meal: Activates glycogenesis (Glucose Glycogen) Deactivates glycogenolysis (Glycogen Glucose) Activates glycolysis (Glucose Pyruvic Acid) Deactivates gluconeogenesis (Pyruvic Acid Glucose) Activates triglyceride synthesis Activates fatty acid synthesis (liver) Thus, insulin deficiency affects the above pathway and as a result: Glycogenesis is not activated Glycolysis is not activated Triglyceride synthesis is not activated Fatty acid synthesis is not activated Jess Q – Week 11 – Can I drink beer? Page 1 In the absence of insulin, the body stays in a fasting state. Therefore, there is no peripheral uptake of glucose by skeletal muscle or storage as muscle glycogen. There is also no protein synthesis or lipogenesis. In above diagram + is stimulation and – is suppresion by insulin . EXPLAIN HOW THE LACK OF INSULIN IN DKA LEADS TO OVERPRODUCTION OF GLUCAGON WITH STIMULATION OF GLUCONEOGENESIS AND LIPOLYSIS Gluconeogenesis: As shown above, a lack of insulin means that rather than in a healthy individual where glycolysis is activated and glycolysis progresses (glucose pyruvic acid), the reverse reaction of gluconeogenesis occurs (pyruvic acid glucose-6-phosphate glycogen) and thus the overproduction of glycogen occurs. Jess Q – Week 11 – Can I drink beer? Page 2 Lipolysis is stimulated: Lack of insulin results in reduction of oxaloacetate production The amount of oxaloacetate available for condensation with acetylCoA is reduced To ensure activation of the TCA cycle, triglycerides are broken down into fatty acyl CoA to Acetyl CoA REFERENCES Colledge, N., Walker, B., & Ralston, S (2010). Davidson’s Principles & Practice of Medicine (21st Edition). Edingurgh: Churchill Livingstone Elsevier. Sherwood, L. (2004). Human Physiology: From Cells to Systems (5th Edition). Australia: Thompson. Lecture notes: Pathophysiology Diabetes (Week 11) Jess Q – Week 11 – Can I drink beer? Page 3