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Endocrinology Lecture 14

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What are the 8 effects of insulin resistance?
Insulin resistance causes 1. visceral obesity 2. atherosclerosis 3. systemic inflammation 4. endothelial dysfunction 5. complex dyslipidemia 6. disordered fibrinolysis 7. hypertension 8. Type 2 Diabetes
What are 4 hormones created by adipose tissue?
Resistin, leptin, adiponectin, tumor necrosis factor TNF-alpha
Where are the 3 places where carbohydrates are found?
Carbohydrates are found in the blood glucose, liver glycogen, and muscles
What is glycogenolysis?
glycogenolysis is the breakdown of glycogen into glucose
What is glycolysis?
glycolysis is the breakdown of glucose into pyruvate and lactate
What is gluconeogenseis?
gluconeogenesis is the creation of glucose from pyruvate or lactate in the liver
What is glycogenesis?
Gycogenesis is the creation of glycogen from glucose in the liver
How many ATPs does glycolysis produce?
Glycolysis produces net 2 ATP
What is hexokinase?
Hexokinase converts glucose into glucose-6-phosphate. This requires ATP
What is phosphofructokinase?
Phosphofructokinase converts Fructose-6-phosphate into Fructose-1,6-biphosphate. This requires ATP
What is pyruvate kinase?
Pyruvate kinase converts phosphoenolpyruvic acid into pyruvic acid which creates 2 ATPs
What happens to pyruvate if there is an oxygen shortage?
Pyruvic acid is reduced to lactic acid so that NAD+ will be available for more glycolysis
What happens to lactic acid?
Lactic acid leaves cell and enters the blood stream. It is taken up by the liver and converted back to pyruvate
What percent of glucose does the brain use?
The brain uses 70% of glucose
What is the normal blood glucose level?
90mg/100ml is the normal blood glucose level
What happens when your body has a low blood glucose level?
Low blood glucose level stimulates the alpha cells of pancreas to produce and release glucagon into the blood stream. Glucagon stimulates liver to break down glycogen into glucose. Blood glucose levels rise.
What happens when your body has a high blood glucose level?
High blood glucose level stimulates the beta islet cells of the pancreas to produce and release insulin into the blood stream. Insulin stimulates cells to take up glucose and stimulates the liver to create glycogen from glucose. Blood glucose levels will lower.
How does somatostatin influence insulin and glucagon?
Somatostatin inhibits glucagon production
Which ANS system stimulates insulin
Insulin secretion is stimulated by the parasympathetic nervous system
Which ANS system stimulates glucagon
Glucagon secretion is stimulated by the sympathetic nervous system
What are the insulin stimulators?
Increased glucose, increased free amino acids, increased GI hormones including gastrin, secretin, CCK, GIP, GLP-1, increased glucagon, noreadrenaline on alpha adrenergic receptors, acetylcholine
What are the insulin inhibitors?
Decreased glucose, increased somatostatin, adrenaline and noreadrenaline on beta adrenergic receptors
What is the effect of insulin on most cells?
Insulin causes protein synthesis in most cells resulting in decreased free amino acids
What is the effect of insulin on the brain
Insulin has no effect on the brain
What is the effect of insulin on muscle?
Insulin causes the muscle to uptake glucose and synthesize glycogen
What is the effect of insulin on liver
Insulin causes the liver to uptake glucose, make glycogen, synthesize fatty acids and decrease glucose synthesis
What is the effect of insulin on adipose tissue
Insulin causes adipose tissue to take up glucose and create glycogen, decrease triglyceride breakdown and increase triglyceride synthesis
What is the glucose transporter in erythrocytes?
GLUT1 is the glucose transporter in erythrocytes
What is the glucose transporter in the brain?
GLUT3 is the glucose transporter in the brain
What is the glucose transporter in the liver and pancreatic beta cells?
GLUT 2 is the glucose transporter in the liver and pancreatic beta cells
What is the insulin sensitive glucose transporter and where is it found/what does it do?
GLUT4 is the insulin sensitive glucose transporter. It is found on muscle and adipose tissue
How many ATP do red blood cells make?
red blood cells make only 2 ATP per glucose molecule bc they have no mitochondria
What two types of cells can make glycogen?
Muscle and Liver
What cell can do both gluconeogenesis, glycogenolysis and glycolysis?
The liver can perform gluconeogenesis glycolysis glycogenolysis and glycogenesis
What is the first irreversible step of gluconeogenesis?
Conversion of pyruvate into oxaloacetate by pyruvate carboxylase in the mitochondria
What is the second irreversible step of gluconeogenesis?
Oxaloacetate is converted into phosphoenolpyruvic acid by PEP carboxykinase
Where is PEPCK made?
Phosphoenolpyruvate carboxykinase is made in the liver in response to low glucose levels
What 4 things affect PEPCK transcription?
Insulin, glucocorticoids, glucagon and thyroid hormone
What 3 enzymes are needed for glycogen breakdown to glucose?
Glycogen phosphorylase, glycogen debranching enzyme, phosphoglucomutase
How do glucagon and epinephrine affect glycogen synthase?
Glucagon and epinephrine activate protein kinase A which phosphorylates glycogen synthase inactivating it.
How do glucagon and epinephrine affect glycogen phosphorylase?
Glucagon and epinephrine activate protein kinase A which activates phosphorylase kinase which phosphorylates glycogen phosphorylase activating it
How does insulin affect glycogen synthase?
Insulin activates protein phosphatase-1 which dephosphorylates glycogen synthase activating it
How does insulin affect glycogen phosphorylase?
Insulin activates protein phosphatase-1 which dephosphorylates glycogen phosphorylase, inhibiting it
What is Von Gierke's disease?
Von Gierke Disease is a Glucose 6 phosphate defect. This results in incomplete gluconeogenesis and subsequently hypoglycemia
What is McArdle's Disease?
McArdle Disease is a skeletal muscle glycogen phosphorylase defect. This results in an inability to breakdown glycogen into glucose in skeletal muscles
What is Hers Disease?
Hers disease is a liver glycogen phosphorylase defect. This results in an inability to breakdown glycogen into glucose in the liver.
What is the result of insulin deficiency?
Insulin deficiency results in hyperglycemia due to too much glucose in the blood stream, increased lipolysis and acidosis as there is not enough glycogen storage, dehydration, polydipsia, hypovolemia,
What are the medical complications to insulin deficiency?
Neuropathy, microangiopathy, retinopathy, nephropathy, foot ischemia, athersclerosis,
What are AGEs?
AGEs are advanced glycation end products (AGEs). AGEs are markedly increased in diabetes because of the excess in glucose availability
What is RAGE?
RAGE are the receptors for advanced glycation end products. When AGEs bind to RAGE, this contributes to many age and diabetes related diseases including atherosclerosis, arthritis, asthma, etc
What are the effects of protein glycosylation?
Protein glycoslyation can change the charge of the protein, change 3d structure of the protein, lead to cross-linking of peptide chains, and change function
What causes Type 1 Diabetes Mellitus?
T cell mediated destruction of beta islet cells of pancreas
What is DPP-4?
DPP-4 inhibits activation of GLP-1. Inhibition of DPP-4 increases GLP-1 activation resulting in insulin production which improves islet function
What is PPAR-gamma?
PPAR-gamma is peroxisome proliferator-activated receptor gamma (PPAR-gamma). It regulates fatty acid storage and glucose metabolism
What is the PPAR-gamma paradox?
Inhibiting PPAR-gamma leads to type 2 diabetes, but inhibiting PPAR-gamma also leads to increased sensitivity to insulin
What are thiazolidinediones?
Thiazolidinediones are a therapy for Type 2 Diabetes. Targets insulin resistance without causing hypoglycemia. Preserves beta cell function and improves cardiovascular outcomes