Endocrine Pancreas and Diabetes Mellitus Flashcards
Describe briefly the chemical structure of insulin and proinsulin, and how proinsulin converted to native insulin
Insulin characteristics:
• ONLY SOURCE is pancreatic beta-cells
• Composed of a 2 chain protein 6000 MW
o Alpha chain & Beta chain linked by disulfide bridges.
The active form (native insulin) is produced from proinsulin.
• Preproinsulin Proinsulin Insulin + C-Peptide
o First synthesized as preproinsulin in pancreatic B cells
o It is taken to the ER and is cleaved, turning into proinsulin.
o Proinsulin folds into correct conformation and 3 disulfide bonds are formed.
Correct conformation is the ring diagram, with the two ends overlapping (the alpha and beta chains), with disulfide bridges forming between them.
• Highly conserved between species
List which tissues in the body require insulin, and discuss how many tissues make insulin
- Insulin faciliatates glucose uptake by most tissues, except RBCS, most of the brain, intestinal mucosa, lens of eye, kidney tubules
- In the liver it converts glucose to glycogen, and inhibits gluconeogenesis.
- In adipose it converts glucose to TGs (triglycerides)
islets of langerhans in the pancreas (specifically beta cells) are the only tissue in the body to make insulin
List the major actions and sites of action of insulin in regulating carbohydrate, lipid, and protein metabolism
Carbohydrate metabolism:
• Liver
o GLUT 2 DOES NOT need insulin for membrane transport of glucose
o Insulin aids in phosphorylation of glucose
Glycogen storage
o Insulin inhibits gluconeogenesis
o Insulin decreases glycogenolysis
o OVERALL effect is to decrease glucose output by the liver.
• Muscle
o Stimulates glucose transport into cell by aiding GLUT 4
o Aids in glycogen storage
• Adipose
o Insulin stimulates glucose transport into cell by aiding GLUT 4
o Insulin aids in esterification of FFA into triglycerides
o Limited conversion of glucose into stored fat.
Lipid metabolism:
• Adipose
o Promotes FFA storage as Triglycerides by inducing “Lipoprotein Lipase”
o Prevents Lipolysis by inhibiting hormone-sensitive lipase
o Stimulates use of ketacids for energy
Protein metabolism:
• Enhances protein and AA sequestration in target tissues, so is considered “Anabolic Hormone” and promotes growth
• Inhibits proteolysis
List the biological stimuli that control the rate of insulin secretion and the effect of these stimuli
Insulin secretion INCREASED by: Glucose** (this is the major stimulator of insulin secretion) Amino acids FFA Ketoacids
Insulin secretion is DECREASED by: Epinephrine Somatostatin Leptin Fasting, Exercise, Endurance training
List the major actions of glucagon, and where glucagon exerts its actions
Glucagon is produced in pancreas cells, its actions include:
• In the liver
o Increases gluconeogenesis
Increases every rate limiting enzyme
o Increases glycogenolysis
If glycogen is present, it’s mobilized.
o Decreases glyconeogenesis
• Increases protein catabolism
• Increases lipolysis
Mechanisms of Glucagon Effects
• Liver (increases glucose output)
• Muscle (Glucagon increases FFA, indirectly inhibits glucose uptake by muscle and fat)
• Adipose tissue (promotes lipolysis)
Describe the major physiological changes that occur in diabetes mellitus
decreased glucose uptake, increased protein catabolism, increased lipolysis leading to:
weight loss, pu/pd, glucosuria (glycosuria), polyphagia, ketoacidosis (sweet smelling breath); cataracts (dogs)
Discuss whether diabetes in dogs and cats is a disease of young or older animals
older; over 50% cats >10 y/o; dogs 7-9 y/o
Describe why obese animals are often resistant to the action of insulin
perpetually high levels of glucose in the blood, constant pressure on beta cells to produce insulin, destruction of beta cells
Describe the “C” fragment of insulin and its clinical use
seen in endogenous insulin; able to determine bodies ability to produce insulin
List factors (and their effects) that modulate insulin secretion
Carbohydrate metabolism:
• Liver
o GLUT 2 DOES NOT need insulin for membrane transport of glucose
o Insulin aids in phosphorylation of glucose
Glycogen storage
o Insulin inhibits gluconeogenesis
o Insulin decreases glycogenolysis
o OVERALL effect is to decrease glucose output by the liver.
• Muscle
o Stimulates glucose transport into cell by aiding GLUT 4
o Aids in glycogen storage
• Adipose
o Insulin stimulates glucose transport into cell by aiding GLUT 4
o Insulin aids in esterification of FFA into triglycerides
o Limited conversion of glucose into stored fat.
Lipid metabolism:
• Adipose
o Promotes FFA storage as Triglycerides by inducing “Lipoprotein Lipase”
o Prevents Lipolysis by inhibiting hormone-sensitive lipase
o Stimulates use of ketacids for energy
Protein metabolism:
• Enhances protein and AA sequestration in target tissues, so is considered “Anabolic Hormone” and promotes growth
• Inhibits proteolysis
Compare the mechanisms and sites of action of glucagon and epinephrine in elevating blood glucose
(insulin and hypoglycemic objectives- note Somogyi rebound)
hyperglycemic; epinephrine inhibits insulin secretion
Describe the role of somatostatin in regulating pancreatic function
IGF-1/produce hyperglycemic state
Distinguish between IDDM and NIDDM
IDDM- Insulin dependent DM: destruction or loss of function of beta cells
NIDDM- non-insulin dependent DM (1/3 cat cases): decreased number or responsiveness of insulin receptors; can be insulin tolerance secondary to obesity or other factors
Describe the major symptoms of diabetes mellitus
PU/PD, glycosuria, weight loss, ketoacidosis, cataracts (dogs) hyperphagia
Describe the major cause of PU/PD in diabetic animals
glucose in kidneys, molecule takes a lot of water with it
Describe the source of glycosuria seen in more severe cases of diabetes
leak out into urine, kidney threshold, differs dog/cat
cat threshold: 240-300 mg/dL
dog threshold: 180-220
