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Pancreas and Adipose Tissue (Insulin (decreases blood glucose…
Pancreas and Adipose Tissue
Pancreas
endocrine pancreas
alpha: produces glucagon
beta: produces insulin
delta: produces somatostatin
gamma: produces pancreatic polypeptide
epsilon: produces small amounts of ghrelin
exocrine pancreas: digestion
digestion and glucose homeostasis
Adipose tissue
largest endocrine organ
adipokines
adiponectin
most abundant hormone in circulation
only secreted by adipose tissue
important regulator of insulin sensitivity
levels decrease with obesity
less adiponectin = insulin resistance
leptin
adipsin
cytokine/chemokines
acute phase proteins
angiotension
PAI-1
Insulin
small protein
decreases blood glucose concentration
inhibits glucagon
stimulates glucose uptake into cells
store glucose as glycogen
inhibits gluconeogenesis
store amino acids as protein
inhibits protein degradation
store fatty acids as fat
inhibits lipolysis (fat sparing)
increased cell permeability to K, Mg, and PO4
regulation
stimulatory
increase in blood glucose concentration
increased aa and fa blood conc
inhibitory
decrease in blood glucose conc
cortisol, glucagon, growth hormone and epi are counter-regulators
secretion
glucose transported in thru GLUT transporter (cell surface receptor)
elevated glucose levels in ECM lead to elevated glucose levels in beta cell
K gate close and Ca gate open
increased IC Ca conc causes insulin release
transporters
hexose transporters (GLUT)
7 types
GLUT4 is most important
for glucose homeostasis
present in cardiac and skeletal muscle and adipose tissue
transport sugars via conformational changes, flipping the transporter between alternate states
Glucagon
synthesized in alpha islet cells
increases blood glucose concentration
stimulates breakdown of glycogen in liver
increases blood fatty acid and ketoacid concentration
stimulates gluconeogenesis
regulation
stimulatory
low blood glucose (hypoglycemia)
elevated amino acids
exercise, stress, epinephrine, CCK, ADH, cortisol
inhibitory
high blood glucose (hyperglycemia)
insulin
somatostatin
Diabetes Mellitus
Type 1 (insulin dependent)
deficiency of beta cell mass from immune destruction
due to viral or genetic causes
more than 50% of canine DM & <10% of feline DM
signs
absolute deficiency of insulin
hyperglycemia (high blood glucose)
antibodies against beta cells
lymphocytes in pancreatic islets
lean body mass, loss of adipose tissue
increased blood aa, fa, and ketoacid conc
ketone production
high levels due to breakdown of fat
lots of ketones signals diabetic ketoacidosis (DKA) which can be fatal
Type 2 (non-insulin dependent)
abnormal beta cell mass and functional insulin secretion
beta cells become exhausted and undergo apoptosis
90% of feline DM
characterized by insulin resistance
strong link to obesity
(3-5x increased risk for DM in obese animals)
deletion of GLUT4 from muscles and/or adipocytes
signs: hyperglycemia, glycosuria, no antibodies against beta cells
can be treated with insulin therapy and by treating underlying obesity
Type 3
secondary to pancreatitis (due to pancreatic destruction)
high levels of insulin antagonizing hormones
cortisol, epi, glucagon, growth hormone, progesterone
Insulinoma
malignant pancreatic tumor
secretes excessive insulin
uncommon
causes insulin shock (life threatening)
extreme hypoglycemia
brain starved for energy
treatment: surgery to remove the tumor
Somatostatin
endocrine and paracrine action
inhibit secretion of growth hormone
inhibits glucagon secretion (paracrine)
decreases rate of nutrient absoprtion
regulation
stimulatory
glucagon
glucose, amino acids, fatty acids
gastrointestinal hormones
inhibitory
insulin (via intra-islet paracrine secretion)