Download 5. Pancreas: Glucagon

5. Pancreas
• has both exocrine (acini secrete digestive
enzymes) and endocrine function (islets of
Langerhans)
• control: responds to blood glucose levels
(humoral)
• hormones are polypeptides (proteins)
http://www.usc.edu/hsc/dental/ghisto/end/c_49.html
5. Pancreas
• major cell types
– alpha cells secrete glucagon
– beta cells secrete insulin
– delta cells secrete somatostatin (which inhibits
insulin and glucagon secretion, and decrease fat
absorption in intestines)
– F cells regulate exocrine function of pancreas
(secrete pancreatic polypeptide)
5. Pancreas: Glucagon
• actions: hyperglycemic (increases blood glucose)
– stimulates formation and release of glucose from liver
(main target)
• glycogenolysis - breakdown of glycogen (storage form
of glucose)
• gluconeogenesis - formation of glucose from
noncarbohydrate molecules (e.g., amino acids,
glycerol, lactic acid)
– stimulates glycogenolysis in skeletal muscle
– stimulates triglyceride breakdown in adipose tissue (fat
mobilization)
5. Pancreas: Glucagon
• control:
– secreted in response to low blood sugar, rising
amino acid levels in blood
– inhibited by increased blood glucose and by
somatostatin
5. Pancreas: Insulin
• actions: hypoglycemic (lowers blood glucose)
– increases transport of glucose into muscle and fat cells
(NOTE: does not increase uptake by brain, liver, or
kidney)
– inhibits breakdown of glycogen and formation of
glucose from amino acids or fatty acids (inhibits
glycogenolysis and gluconeogenesis)
– promotes formation of glycogen (liver, skeletal
muscles), protein synthesis (muscle), and fat synthesis
and storage (adipose)
5. Pancreas: Insulin (Control)
• stimulated by:
– increased blood glucose
– increased blood amino acid and fatty acid levels
– parasympathetic impulses
– hyperglycemic hormones (GH, glucagon, epinephrine,
thyroxine, glucocorticoids) indirectly result in insulin
secretion by increasing blood glucose levels
• inhibited by:
– low blood glucose and by somatostatin
– sympathetic impulses
5. Pancreas: Insulin - Disorders:
Diabetes Mellitus (DM)
• hyposecretion (or hypoactivity) of insulin
• body cells not stimulated to take up glucose
• hyperglycemia (excess blood glucose)
– very high glucose --> nausea --> fight-or-flight response -->
secretion of hyperglycemic hormones (epi, NE [adrenal
medulla], glucocorticoids [adrenal cortex]) --> stimulates
gluconeogenesis, lipolysis, glycogenolysis --> adds to
already high glucose
– not all sugar reabsorbed from urine --> glucose lost in urine
(glucosuria) --> increased water loss --> excessive urine
production (polyuria) and excessive thirst (polydipsia)
5. Pancreas: Insulin - Diabetes Mellitus
• cells use fats as energy source (due to poor glucose uptake)
• hyperglycemic hormones stimulate fat mobilization --> fats
in blood (lipidemia) --> increase in lipid metabolites in blood
(ketone bodies, which are strong organic acids) --> decrease
blood pH (ketoacidosis) and ketone bodies in urine
(ketonuria)
– decreased blood pH --> severe depression of nervous
system --> deep breathing --> diabetic coma --> death
• polyphagia (excessive hunger) - final sign, due to use of fats
and proteins as energy sources
Type I Diabetes mellitus
• also called insulin-dependent diabetes (IDDM; formerly
juvenile onset diabetes)
• onset is sudden, usually before age 15
• may be due to autoimmune attack of proteins in beta cells
result is lack of insulin activity
• lipidemia (high blood lipid content) and increased
cholesterol lead to long-term vascular problems
(arteriosclerosis, strokes, heart attacks, renal shutdown,
gangrene, blindness)
• treated with insulin injections or pancreatic islet
transplant (newer technique)
Type II Diabetes Mellitus
• non-insulin-dependent (NIDDM; formerly mature-onset
diabetes)
• usually starts after age 40
• insulin levels are normal or elevated, but peripheral tissue
become less sensitive to it
• 25-30% of Americans carry gene that predisposes them to
NIDDM, more likely in over-weight people (~90% of cases)
– adipose cells secrete tumor necrosis factor alpha that
depresses production of protein needed for glucose uptake
• often controllable with diet and exercise
Hyperinsulinism
• excess of insulin (usually from injection of excess)
• causes hypoglycemia --> secretion of hyperglycemic
hormones (to raise blood glucose) - low glucose to brain -->
anxiety, nervousness, tremors, weakness --> eventually,
disorientation, convulsions, death due to “insulin shock”
• treated by providing sugar source