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Transcript
Metabolic Pathways - absorptive Metabolic Pathways - postabsorptive GI tract Liver Glucose Glycogen Triglyceride Blood Glucose Glucose Amino Acids Lactate & pyruvate Liver energy Glycogen energy Fatty acids α-ketoacids α-ketoacids amino acids Triglycerides energy glycerol Fatty acids Glucose Glucose Nervous tissue ketones amino acids Fatty acids ketones energy Glucose Glucose amino acids Glucose protein energy Glycogen muscle Fatty acids Triglycerides All tissue adipose Lactate & pyruvate amino acids glycerol protein Glycogen muscle Fatty acids Triglycerides Fatty acids All other tissue adipose Sources of blood glucose 1. Absorptive state is about Glucose storage • • • Glycogen by muscle & liver Triglycerides by adipose All tissues use glucose as the energy source 2. Postabsortive state is about preserving glucose for the nervous system • • Utilizing glucose stores to produce blood glucose Switching other tissues to fat 1. Glycogenolysis • • • Breakdown of glycogen to glucose Liver and muscle Muscle is indirect via lactate & pyruvate 2. Lipolysis • Breakdown of trigylcerides in adipose 3. Gluconeogenesis • Production of ‘new’ glucose from any precursor 1 Hormonal Control of Blood Glucose What controls: • production of glycogen, protein and triglyceride during absorption? • Use of glucose during absorption and the switch to fat postabsorption? • Glucose uptake by liver during absorption and release of glucose postabsorption Insulin • Stimulus for secretion is high blood glucose • Secreted by β cells • Leads to glucose uptake and storage in liver, muscle and fat tissue. • Effect is to ↓ blood glucose Hormonal Control of Blood Glucose • Endocrine pancreas – Only 2% of entire pancreas, – the rest produces digestive enzymes (exocrine) – Islets of Langerhans • Insulin (β cells) • Glucagon (α cells) • Somatostatin (Δ cells) Control of insulin secretion ↑ Blood glucose Sympathetic NS or Epinephrine ↑ Blood amino acids GIP from GI tract β cells Parasympathetic NS 2 How does glucose control insulin secretion from β cell? Blood glucose depolarization Effects of Insulin Muscle and Fat Tissue • Insulin initiates transfer of glucose transporters to cell membrane Glut2 ↑ Glucose transporters → ↓ blood glucose → ↑ production of glycogen K+ channel glucose Ca++ Ca++ dependent release of Insulin containing vesicles Glucose 6 phosphate Glycolysis & Citric acid cycle ATP ↑plasma insulin Effects of Insulin Liver Effects in Muscle & Fat GLUT4 Glycogen synthesis Glucose transporter glucose SNARE dependent transport Glucose transporter • insulin stimulates the synthesis of an enzyme (glucokinase) • Required to ‘trap’ glucose in the cell • initiates glycogen production storage vesicle Insulin 3 Summary of response to insulin Effects in Liver ↑ Plasma insulin GLUT2 Glycogen synthesis Glucose transporter glucose muscle ↑Glucose uptake ↑Amino acid uptake ↑Glycogen & protein synthesis X fat ↑Glucose uptake ↑Triglyceride synthesis liver ↑Glucose uptake ↑Glycogen synthesis ↑Triglyceride synthesis Glucose 6-phosphate glucose glucokinase ↓ Plasma insulin ‘trapped’ muscle ↓ Glucose uptake Glycogen breakdown protein breakdown fat ↓ Glucose uptake Triglyceride breakdown & release of glycerol and fatty acid liver ↑Glucose release into blood due to glycogen breakdown & gluconeogenesis ↑Triglyceride synthesis ↑Ketones released Glucagon • Notable other effects of insulin – Increase amino acid uptake into muscle cells – Insulin receptors in the central nervous system (hypothalamus) – potential role in regulating food intake – Secretion stimulated by low blood glucose – Activates enzymes for gluconeogenesis and glycogenolysis – Leads to ↑ blood glucose levels 4 Glucose Regulation Summary Glucagon Control • primarily under inhibitory paracrine control by insulin • Also sympathetic NS can ↑ glucagon release • Endocrine pancreas • Secretion of several hormones important for blood glucose regulation • Insulin → glucose uptake and storage – Different effects on liver and muscle & fat insulin • Glucagon → glucose production β α • Diabetes – 2 million Canadians – $9 billion per year health care costs – Insulin isolated by Banting & Best 1922, U of T Dept of Physiology (1923 Nobel Prize) • Type 1 – No or very little insulin produced • Type 2 – Reduced cellular response to insulin • Consequences – – – – Death Blindness Kidney disease Limb amputation 5
