Physiological role of insulin

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Physiological role of insulin

• Release of insulin by beta cells
• Response to elevated blood glucose level
• Effects of insulin
• Somewhat global
• Major effects on muscle, adipose tissues, and
  liver
• Increased glucose uptake
• Glucose
• Energy source
• Glycogen synthesis

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• Increased hepatic glycogen synthesis
• Increased glycogen synthase activity
• Increased synthesis of glucose-6-P
• Prevention of glucose release

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• Effects on adipocytes
• Glycerol synthesis
• Increased glucose metabolism
• Increased lipoprotein metabolism
• Lipoprotein lipase
• Increased free fatty acids release
• net results
• Increased triglyceride synthesis

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• Effects on adipocytes
• Enzymes activated by insulin
• Citrate lipase
• Acetyl-CoA carboxylase
• Fatty acid synthase
• Glycerol-3-phosphate dehydrogenase

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• Effects on muscle
• Increased transport of glucose and amino acids
• Increased synthesis of proteins
• Energy from glucose
• Maintenance of potassium homeostasis
• Increased K uptake
• Extreme concentrations of insulin
• Extracellular hypokalemia

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Mechanism of insulin action

• Insulin receptor
• Similar to type I IGF receptor
• Two sets of subunits (alpha and beta)
• Insulin binding
• Alpha
• Receptor tyrosine kinase
• Beta
• Phosphorylation of intracellular domain
• Docking sites for intracellular proteins
• Insulin receptor substrate-1 (IRS-1)

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• Phosphorylation of IRS-1
• Secondary messenger system
• Somewhat complicated
• Ca ions
• PKA
• PKC
• Activation of glucose transport system

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• Effects on glucose transport system
• Glucose transport
• Facilitated diffusion
• Diverse
• Types of proteins
• Tissue-dependent distribution pattern
• Evolved to accommodate specific energy needs

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Physiological role of glycogen

• Decreased blood glucose level
• Insulin-induced
• Subsequent elevation of glucose
• Glycogen break-down
• Gluconeogenesis
• Glycogen
• Antagonistic to insulin
• Gluconeogenesis
• Glycogen break-down

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• Glycogen break-down
• Short-term maintenance of glucose level
• Gluconeogenesis
• Long-term
• Exercise
• Fasting
• Neonates

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• Effects on amino acid and lipid metabolism
• Used as precursor for gluconeogenesis
• Amino acids
• Glycerol
• Lipolysis
• Release of free fatty acids and glycerol
• Substrate for glucose synthesis
• Occurs when insulin concentrations are low
• Potent inhibitor of lipolysis

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• Undernutrition/fasting
• Prevention of hypoglycemia
• Reduced insulin level
• Elevated glucagon
• Adrenal catecholamines
• Critical if glucagon is low

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Mechanism of glucagon action

• Target organs
• Liver
• Adipose tissues

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• Interaction of glucagon with its receptor
• Increased cAMP production
• Activation of PKA system
• Glycogen break-down
• Gluconeogenesis
• Lipolysis
• Inhibition of ketone formation from free fatty
  acid metabolism by liver
• Glucose sparing effects (use of fatty acids as
  energy source)

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Control of pancreatic islet function

• Several factors
• Hormones
• Nervous system
• Metabolic signals
• Blood glucose level
• Most important
• Hyperglycemia
• Stimulation of insulin secretion
• Inhibition of glucagon synthesis

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• Adrenal and neural catercholamines
• Adrenal epinephrine
• Inhibition of insulin secretion
• Alpha receptor-mediated
• Glucose availability during stress
• Stimulation of glucagon secretion
• Epinephrine and norepinephrine
• Activation of beta receptors

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• Amino acids and other metabolites (acetoacetic
  acid)
• Increased insulin secretion
• Protein synthesis
• Fatty acid synthesis
• Increased glucagon secretion
• Prevention of hypoglycemia
• Counteracts effects of insulin
• Abolished when CHO and proteins are ingested
  together

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• Stimulation by GI tract (entero-insular axis)
• Secretion of gastrointestinal inhibitory peptide
  (GIP) and glucagonlike peptide 1 (GLP-1)
• Response to orally ingested glucose
• Stimulates secretion of insulin
• GLP-1 stimulates cAMP production
• Secretion of insulin above the level secreted in
  response to glucose alone
• Beta cells must be competent to respond to
  increased glucose level

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• Stimulation by GI tract (entero-insular axis)
• Secretion of gastrointestinal inhibitory peptide
  (GIP) and glucagonlike peptide 1 (GLP-1)
• Inhibition of glucagon secretion
• Elevated glucose level
• Elevated insulin level

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• Neural control
• Vagus nerves
• Stimulate insulin secretion
• Endocrine factors
• Glucose homeostasis
• GH
• Diabetogenic (stimulates insulin secretion but
  reduces peripheral insulin sensitivity)
• Glucocorticoids

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Glucose counterregulation

• Glucose
• Primary energy source for brain
• No gluconeogenesis
• No glycogen
• No regulatory mechanisms for level of uptake
• Prevention of hypoglycemia
• Decreased insulin secretion
• Increased glucagon secretion
• Release of epinephrine