Always in motion is the future.

Week 6: Endocrine/Reproductive

Pancreas

Updated by Tracey 16 August 02

Function: control circulating glucose levels. Glucose is the ONLY energy substrate the brain, retina and germinal epithelium of the gonads can use efficiently.

Insulin

Insulin secretion is based on blood glucose levels, and can be controlled by some amino acids. Insulin binds with surface receptors with portions penetrating the cell membrane. The receptor portion in the cell autophsophorylates and phosphorylates other intracellular enzymes (activating some, deactivating others). End effects of insulin stimulation:

Insulin secretion increases membrane permeability to glucose in most cells, and of aa's, K⁺, and P⁺. It also has slower effects based on enzyme phosphorylation, mRNA translation and DNA transcription.

Insulin and Carbohydrate Metabolism

Insulin causes rapid uptake, storage and use of glucose. Body normally depends on fatty acid for most energy requirements. Effects of Insulin Secretion...

Muscle: increases glucose permeability of membrane. Cell uptake -> usage (or storage as glycogen if not active). Heavy activity has same effect as insulin on membranes.
Liver: Causes glycogen formation and storage.
Inactivates liver phosporylase, increases glucokinase activity, which causes glucose phosphorylation -- phosphorylated glucose cannot diffuse back through the membrane, stimulates glycogen synthesizing enzymes. Excess glycogen -> conversion to fa's -> triglycerides transported to adipose

Between meals, pancreas decreases insulin secretion.
phosphorylase -> glycogen split -> glucose phosphate
glucose phospatase -> phosphate radical split from glucose -> glucose diffuses out.
Brain: already permeable to glucose, insulin does not effect. Brain uses glucose for energy. Blood glucose levels are maintained mainly to "feed" the brain. Low blood sugar (20-50mg/dl) -> hypoglycemic shock -- progressive nervous irritability, fainting, convulsions, coma.
Other cells: same as in muscle.

Insulin and Fat Metabolism

Excess Insulin:
inc. glucose use -> dec. fat use + fat synthesis & storage
Insulin inhibits lipase which causes triglyceride hydrolysis, so fatty acid release is also inhibited. Glucose transport into fat cells provides glycerol for triglyceride formation.

No Insulin:
lipase activates triglyceride hydrolysis -> inc. [plasma ffa's] available for energy substrate.
phospholipid & cholesterol formed -> atherosclerosis.
liver fa's form too much acetoacetic acid -> acidosis -> coma -> death.

Insulin and Protein Metabolism

Insulin promotes protein formation:

causes active aa transport into cells
enhance mRNA translation on ribosomes
long-term inc. of DNA transcription of selected sequences, especially enzymes for carbohydrate, fat and protein storage
inhibits protein catabolism, decreasing aa release from cells

Works synergystically with growth hormone. Thought to promote cellular uptake of different aa's.

Glucagon

Many functions opposite to those of insulin, including increasing [blood glucose]. Two major effects:

Glycogenolysis: breakdown of liver glycogen.
Activate adenyl cyclase -> cyclic AMP formed -> activate protein kinase regulator protein -> activate protein kinase -> activate phophorylase b kinase -> phosphorylase b converts to phosphorylase a promoting glycogen degradation to glucose-1-phosphate -> dephosphorylated and released from liver.
Gluconeogenesis: making glucose from other stuff
activate aa transport and gluconeogenesis enzymes to maintain hyperglycemic state

Secreted when blood sugar lowers. High [aa] also stimulates glucagon secretion -- aa's rapidly converted to glucose making it available to the tissues.

Diabetes Mellitus

Usually a result of dimished insulin secretion. Genetic factors can increase susceptibility of beta cells where insulin is formed to viruses, or autoimmune antibodies against the beta cells, or hereditary tendency for beta cell degeneration. Obesity also decreases insulin receptors in target cells.

Pathology:
decreased glucose utilization -> inc. [blood glucose]
increased fat mobilization -> abnormal fat metabolism & cholesterol deposition & atherosclerosis
protein depletion
diuresis -- glucose loss in urine causes water loss from osmosis -> dehydration
acidosis from excess fat metabolism

Treatment:
Insulin injection with normal diet. Low carbohydrate diets addressed [blood sugar] but not abnormal fat metabolism, which is associated more with vascular problems, susceptibility to infection, eye problems, hypertension and chronic renal disease.