Insulin 1 - Diabetes overview Flashcards
(31 cards)
How much glucose does the body require per day?
Minimum of 190 mg of glucose/day
What is the end result of uncontrolled diabetes mellitus?
Cardiovascular disease (macrovascular effects)
Neuropathy, nephropathy, retinopathy
Hyperlipidemias
Peripheral vascular disease
Signs/symptoms of DM?
Polyuria, polydipsia Weight loss Random plasma glucose over 200 Fasting glucose over 126 Glucose tolerance test over 200 mg/dL 2 hours after ingestion A1c over 6.5%
What is Type 1 DM? Why is type 1 DM considered autoimmune in some cases?
Loss of B cells
Requires exogenous insulin for survival
It’s an autoimmune disease (type 1A is 90%)
80% of patients have antibodies to islet cell antigens at time of diagnosis, antibodies are directed to both cytoplasmic and membrane bound antigens as well as insulin
There is also non-immune or idiopathic type 1 (type 1B 10%)
What is Type 2 DM?
Insulin resistance, decreased release of insulin
20-30% of patients require insulin in addition to PO meds
What is Type 3 DM?
DM caused by secondary factors
Specific genetic defects in B cell function or insulin actions
Decreased insulin in the CNS could be linked to Alzheimers?
What is Type 4 DM?
Gestational DM
Occurs in 4% of pregnancies
Increases risk of T2DM in the mother after birth as well
What is the major morbidity associated with Type 1 DM?
Renal failure
What is the major morbidity associated with Type 2 DM?
Macrovascular disease
Risk factors for Type 1 diabetes?
Genetic (HLA Class II genes DR and DQ - 40 to 50% of risk)
Viruses (Enterovirus - coxsacki B related to polio and rhinovirus)
Family history (40-60% concordance in twins, although 75% do not have a family member with T1DM)
Risk factors for Type 2 diabetes?
Family history - genetics (4 fold increase in risk if have a family member with DM)
Ethnicity (African American, Latino, Native American, Asian American, Pacific Islander)
Obesity ~80% of affected individuals
Life style (Metabolic syndrome)
What is the function of A (alpha) cells in the pancreas?
Makes up 20% of cells in pancreas
Function is to mobilize fuel via gluconeogensis and glycogenolysis in the liver
Secretory products are proglucagon and glucagon, which increase the breakdown of glycogen/release of glucose to increase glucose levels in the bloodstream
What is the function of B (beta) cells in the pancreas?
Makes up 75% of cells in the pancreas
Promotes fuel storage and promotes growth
Secretes proinsulin, insulin, C-peptide, and amylin (to increase glucose storage)
What is the function of D (delta) cells in the pancreas?
Makes up 3-5% of cells in the pancreas
Inhibits secretory cells
Secretes somatostatin (inhibits insulin and glucagon excretion)
What is the function of F (PP) cells in the pancreas?
Makes up less than 2% of cells in the pancreas
Facilitates the digestive processes
Secretes pancreatic polypeptide
What occurs in the islets of langerhans in T2DM?
Alpha cell dysfunction results in secretion of inappropriately high levels of glucagon
Fewer beta cells, so you have insufficient secretion of insulin
How much pancreatic function is lost at time of diagnosis?
50% of normal
How is insulin made? How is it stored?
Proinsulin is converted to insulin and C-peptide in the golgi apparatus
It’s 51 amino acids in 2 peptide chains (A and B) linked by disulfide bridges
Stored in Beta cells as 2 atoms of zinc and 6 molecules of insulin
What is C-peptide?
Insulin and C-peptide are released in equal amounts in response to elevated glucose
C-peptide has no known function but can be used as an index of insulin secretion
How is insulin removed from the body?
It is degraded via hydrolysis of disulfide bonds then proteolysis (by insulinase)
Liver clears ~60% and kidneys clear the other 40%
Half life is 3-9 minutes
Describe the mechanism of insulin release?
Pancreas is exposed to increased glucose, binds to GLUT-2 transporters on beta cells. Glucose is internalized and oxidized to ATP via the TCA cycle.
Increased ATP levels causes ATP-dependent K+ channels to close, which depolarizes the cell, opening voltage gated Calcium channels.
Calcium rushing in stimulates the exocytosis of insulin granules into the blood
How do sulfonylureas work in the release of insulin?
They block ATP dependent K+ channels, thus depolarizing the cell and opening Ca++ channels to stimulate insulin release
Describe the mechanism of insulin action
Insulin stimulates glucose uptake into target tissues by activating GLUT4 receptors
Insulin initiates phosphorylation cascade within the cells, translocates glucose transporters from inside cell to the cell surface
Glucose enters via facilitated diffusion through transporters
The glucose is then used for energy or stored
Where are GLUT1 transporters found? What is their function?
GLUT1 transporters are found in all tissues, red blood cells and brain
Function - basal uptake of glucose, transport across the BBB
