Biological effects of GH

• Somatotropic– Growth and cell proliferation

• IGF-I mediated

• Metabolic– Direct action of GH

• IGF-I independent• Many tissues• All nutrients

• Effects of GH on metabolism– Nutrient partitioning

• After absorption– Independent of digestion process– Independent of nutrient expenditure

Nutrient partitioning during growth

• Alteration of growth by exogenous GH– Alteration in nutrient partitioning between

muscles and adipose tissue• Increased daily gain• Increased feed efficiency• Decreased fat deposition• Increased protein deposition

– Age-dependent response

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• Action of GH– Different between adipose and muscle– Growth of muscle in response to GH

• Depends on availability of dietary proteins and energy

• Involves IGF-I

– Decreased fat accumulation• Inhibition of glucose uptake

• Action of GH– Decreased fat accumulation

• Inhibition of glucose utilization• Glucose diverted to muscles • Net results

– Decreased adipocyte hypertrophy– Increased muscle growth

Effects on adipoccytes

• Chronic

• Lipogenesis– Inhibited

• Fatty acid synthesis

• Lipolysis– Stimulated when undernutrition

• Mechanism– Inhibition of insulin action on adipocytes

• Decreased sensitivity of adipocytes to insulin stimulation

– Decreased glucose usage by the cells– Independent of receptor number or intracellular

signaling system

• Inhibition of fatty acid synthase expression– Interference with insulin signaling pathway– Direct genomic effects

• Effects on lipolysis– Indirect mechanism

• Alteration of adipocyte responsiveness to acute lipolytic signaling pathway

• Highly dependent on nutritional status of the individual

• Increased hepatic gluconeogenesis– Direct effects– Inhibition of insulin action

• Increased efficiency of amino acid utilization– Reduced oxidation– Results in muscle fiber hypertrophy

Pancreatic hormones

Pancreas

• Exocrine organ– Digestive enzymes

• Discovery of the first hormone (secretin)

• Endocrine organ– Islets

• Described by Langerhans

– Islet of Langerhans

• Cell composition– Two major types

• Alpha– Glucagon

• Beta– Insulin

– Other cells• D cells (SS)• F cells (pancreatic

polypeptide)

Regulation of glucose metabolism

• Glucose homeostasis– Movement of glucose into and out of

extracellular space• Involvement of many tissues

– Liver– Adipose tissue– Muscle

• Two hormones– Insulin– Glucagon

Regulation of glucose metabolism

• Glucose homeostasis– Basic concept

• Coordinated relationship between alpha (glucagon) and beta (insulin) cells under control of glucose sensor

Regulation of glucose metabolism

• Glucose homeostasis– Basic concept

• Particular arrangement of cells within the islet

• Specialized cell membrane

Insulin

• Required for normal growth and development

• Only hormone that can lower blood glucose level– Dominant metabolic regulator

• Unregulated glucose level if absent• Hypoglycemia if too high

– Cause neural shock

• Biochemistry– Two subunits

• Alpha and beta• Linked by two disulfide

bridges

– Synthesized as prohormone

• Preproinsulin– Proinsulin precursor

• Proteolytic cleavage– Proinsulin– Formation of disulfide

bridges

• Insulin– Coupled with zinc within the beta cells– Very short life

• Around 5 to 15 min after synthesis• Metabolized by kidneys and liver

Glucagon

• Biochemistry– Single peptide

• 29 AA• Similar structurally to

gastric inhibitory peptide and VIP

• Cleaved from larger protein

• Highly conserved– Identical among

mammals

Other pancreatic peptides

• SS– Localized in D cells

• Located adjacent to alpha and beta cells– Local action of SS

– Affects function of intestine• Movement of nutrients

• Pancreatic polypeptide– Unclear function in mammals

• Suppression of SS secretion by pancreas and intestine

• Inhibition of gallbladder and pancreatic enzyme secretion

– Secretion affected by nutrient uptake by the intestine