Transcript Biological effects of GH

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
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Increased daily gain
Increased feed efficiency
Decreased fat deposition
Increased protein deposition
– Age-dependent response
• 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