Jan 20 - Hormones of the pancreas and intermediate metabolism Flashcards
Name the hormones for glucose metabolism. Where are they secreted from?
The pancreas secretes insulin and glucagon
The adrenal gland secretes cortisol and epinephrine
The pituitary gland secretes growth hormone
Which hormone(s) reduce(s) blood glucose?
Insulin
Which hormone(s) raise(s) blood glucose?
Glucagon, cortisol, epinephrine, growth hormone
What is considered a normal insulin level?
5-6 mmol
Describe the histology of the pancreas
The pancreas is made up of two cell types: endocrinic islets of Langerhans and exocrinic acini. The islets make up about 15-20% of the pancreas. The acini make up the remainder of the pancreas and they secrete digestive enzymes into the duodenum.
What are the different cell types of the islets of Langerhans? What do they secrete?
Alpha cells secrete glucagon
Beta cells secrete insulin
Delta cells secrete somatostatin
F cells secrete pancreatic polypeptide
Describe insulin (and proinsulin)
Proinsulin is made up of three chains: A chain, B chain and C chain. C peptide has no known function and proinsulin as little biological activity. A and B chains are connected by two disulfphide covalent bonds between cysteine residues. Posttranslational processing occurs in the Golgi and secretory granules. The C chain is cleaved away by proprotein convertase. Mature insulin (complexed with Zn++) and the C peptide are released from granules by exocytosis
Name stimulants of insulin release
Sugars (glucose, mannose)
Amino acids (leucine)
Vagus nerve stimulation (ex. if you smell food)
Sulfonylureas
Name amplifiers of glucose-induced insulin release
Enteric hormones (e.g., gastrin, secretin, cholecystokinin) Neural amplifiers (beta-adrenergic effect of catecholamines) Amino acids (arginine)
Name inhibitors of insulin release
Neural (alpha-adrenergic effect of catecholamines)
Humoral (somatostatin’s paracrine action)
What does insulin promote?
Glucose uptake into cells (liver, adipose, muscles)
Glycogen synthesis (liver)
Lipid synthesis (adipose)
Protein synthesis by increasing amino acid uptake
Thus insulin is anabolic
What is responsible for glucose uptake into cells
Glucose uptake into cells is mediated by facilitated diffusion using glucose transporters: GLUT1 through GLUT5
Describe GLUT1
It’s found in the brain endothelium (it’s not sensitive to insulin)
Describe GLUT2
Release glucose from cells (liver, fat, muscle)
It is not sensitive to insulin
It acts as “glucoreceptors” in beta cells to release insulin
Describe GLUT3
Found in neurons (not sensitive to insulin)
Describe GLUT4
Very sensitive to insulin in uptaking glucose into cells
Describe GLUT5
Found in the gut (responsible for the uptake of ingested glucose)
Describe glucagon
It is produced by alpha cells of the islets of Langerhans
It’s potent releaser of glucose
It stimulates gluconeogensiss (production of glucose from non-glucose sources)
Stimulates lipolysis
What is diabetes mellitus?
A syndrome of disordered metabolism with inappropriate hyperglycemia due to:
- a deficiency of insulin, or
- a reduction in effectiveness of insulin, or
- both
What are two types of diabetes mellitus?
Type I and type II
Describe type I diabetes mellitus
It’s caused by the destruction of beta cells. It’s prevalence is about 10. Insulin levels are low to absent
Describe type II diabetes mellitus
It’s a metabolic syndrome. It’s prevalence is about 80-90%. Early on, the insulin levels are normal to high, but as the disease progresses, they become low. 85% of type II DM patients are obese
What does insulin deficiency cause?
Decreased glucose uptake
Increased hepatic gluconeogenesis
Increased lipolysis and ketone
Increased protein breakdown
What does decreased glucose uptake cause?
Hyperglycemia, glycosuria, osmotic diuresis > dehydration, loss of electrolytes > cardiovascular depression > shock, coma, death (also caused by dehydration and loss of electrolytes)
What does increased hepatic gluconeogensis cause?
Same thing as decreased glucose uptake
What does increased lipolysis and ketone cause?
Ketosis, acidosis > vomiting/cardiovascular depression > dehydration, loss of electrolytes > shock, coma, death
What does increased protein breakdown cause?
Nitrogen loss in urine
What does glucose toxicity cause?
Glucose toxicity - oxidative stress due to increase in oxygen radicals; alterations of protein glycosylation (glycation) and functions (e.g. glycated haemoglobin, HbA1c)
What are chronic complications due to diabetes mellitus?
Opthalmologic complications (diabetic retinopathy, cataracts) Renal complications (diabetic nephropathy, infections) Neurological problems (diabetic neuropathy - sensory, motor, autonomic) Cardiovascular defects (cardiomyopathy, myocardial infarction)
What is the primary treatment for type I diabetes mellitus?
Insulin, nature of dietary intake
What is the primary treatment for type II diabetes mellitus?
Nutritional therapy - weight loss (diet, exercise)
Pharmacological therapy
What are different pharmacological therapies available for the treatment of type II diabetes mellitus?
Biguanides Sulfonylureas Other secretagogues Thiazolidinediones Glucosidase inhibitors Insulin
What are biguanides? Give an example
Hypoglycemic agents that inhibit gluconeogensis. Ex. Metformin
What are sulfonylureas?
Insulin secretagogues (ex. glyburide)
What is an example of another secretagogue?
Repaglinide
What are thiazolidinediones?
They increase sensitivity to insulin (ex. rosiglitazone)
What are glucosidase inhibitors
Inhibit digestion of complex carbohydrates, hence reduce sugar availability (ex. acarbose)
