Lecture 15: Importance of GH, Insulin and Glucagon Flashcards
What do GH, insulin and glucagon have in common?
-3 are important for partition of nutrients
Review: What does the GH do?
-GH (somatotropin) originates from cells of the anterior pituitary
-Promotes tissue and body growth in young animals, especially longitudinal growth until skeleton is complete
-In adults, GH mainly controls metabolism
-Protein sequence differs a lot b/w species (poor cross reactivity)
Ex bovine hormone vs human repeater will be minimal bc of point above
How s GH regulated and what does it stimulate?
-GH secretion is regulated by hypothalamic neurohormones:
-GHRH stimulates GH
-GHIH (somatostatin) inhibits GH
-GH stimulates IGF1 production by the liver, in turn IGF1 stimulates cartilage and bone growth and milk production
-GH regulates lipid and proteins metabolism
-GH receptor is a member of the interleukin (cytokine) family
How is GH secretion regulated?
-Very precise dual regulation by hypothalamic GHRH and GHIH
-Hypothalamus receives info from external stimuli and nutrients in the blood:
-Follows a circadian pattern, increase during sleep
-High AA and low glucose content in plasma both increases GH secretion (high protein diet, long fasting)
-Exercising and stress also increases GH secretion
-Sex steroids increase GH secretion = burst of growth at puberty
-IGF1 responsible for neg feed back on GH secretion
What are direct effects of GH?
-GH affects most cells of the body (responds to most receptors in body)
-GH has a short half life (around 20min)
-GH is an anabolic hormone: like insulin GH promotes synthesis of protein
-GH also a catabolic hormone: conversely to insulin GH stimulates lipolysis (breakdown fat to release AA) and reduces lipogenesis (formation of fat) in adipose tissue (important during fasting and at night)
-Lipolysis increases fatty acid production. in addition, GH decreased glucose utilization in most tissues as a result GH increases glucose concentration in blood
(purpose for using it for dairy cow in late lactation)
What are the indirect roles of GH via IGF’s?
-GH stimulates synthesis of IGF1 and its binding proteins in the liver. Small amounts also locally produced in muscle and adipose tissue
-IGF1 is a polypeptide chain with a sequence similar in human, porcine and bovine. Bound to carrier proteins its half life is much longer than GH
-It acts via its own tyrosine kinase receptor
-IGF1 stimulates chondrocytes (cartilage cells) proliferation to increase bone growth
-IGF1 stimulates satellite cells in muscle (muscle fibre growth)
-IGF1 stimulates AA uptake and protein synthesis
How does GH relate to lactation?
-No major role in mammary gland development
-Effects of GH on milk production are mainly mediated via metabolism, and partitioning nutrients to the mammary gland for milk synthesis
-Insulin normally directs nutrients towards lipogenesis in adipose tissue. GH has the opposite effect
-Bovine GH (bST) can boost milk production by 10-40% in early and late lactation, respectively
-Major concern for humans: infant can absorb GH and IGF in the gut, IGF1 has similar sequences in bovine and human
(risk would be with IGF1 in infants)
What is the consequence/pathology of an overproduction of GH?
-Rare in animals
-Before puberty (before skeletal formation) can result in gigantism: increased longitude growth essentially tall individuals with long limbs
-After puberty (no more longitudinal growth) can result in acromegaly: increased bone width and density (thick hands and thick/boney head), diabetes
-In old dogs and cats: can be due to pituitary tumor
What is the consequence/pathology of having a lack of GH production?
-Dwarfism
-Mostly genetic defects of GH or GH receptor genes, can be treated by injection of recombinant GH and IGF1 (artificially create)
-In dogs, dwarfs keep their puppy coat for along time, lack of IGF1 action on hair follicle differentiation
(problem with receptor GH won’t help so IGF1 is given)
Where are insulin and glucagon produced?
-Pancreas is an endocrine and exocrine (release some towards ‘outside’ ie stomach) gland
-Endocrine pancreas: islets of langerhans (scattered through the pancreas)
-In islets: βcells (70%) secrete insulin, α cells (20%) secrete glucagon
TRUE OR FALSE: Insulin and glucagon have opposite effects on glucose metabolism
TRUE
What is the synthesis and secretion of insulin?
-Produced as a pre hormone, converted to proinsulin
-Before secretion, converted to active insulin by removing a connecting (C)-peptide
-After secretion, circulates free (half life 5-8min short) and is degraded in target cells or in liver (not intended to have a long lasting effect so if want more have to produce more)
What is the synthesis and secretion of glucagon?
-29 AA peptide produced as a pre hormone readily converted to active glucagon
-After secretion, circulates free (half life 5min) and is metabolized in the liver and kidney
What are the actions of insulin?
-Insulin is the major anabolic hormone of the body
-Through its tyrosine kinase receptor, insulin leads to the up regulation of membrane glucose transporters –> CELLULAR UPTAKE OF GLUCOSE in muscles and adipose tissue
-Insulin stimulates incorporation of glucose in energy storage molecules: glycogen in liver and muscle, and triglycerides in adipose tissue
-Insulin also promotes the uptake of AA
-The overall effects will lead to a decrease in blood glucose and AA levels
What are the actions of glucagon?
-Glucagon has opposite effect to insulin
-Through its G-protein coupled receptor glucagon actives enzymes responsible for glycogenolysis–> release of glucose from glycogen by the liver
-Glucagon also stimulates gluconeogenesis in the liver (synthesis of glucose)
-Glucagon stimulates release of fatty acids from triglycerides in adipose tissue
