Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
22 Cards in this Set
- Front
- Back
|
What is metformin's (biguanide) mechanism of action?
|
Metformin acts to inhibit hepatic glucose release (no gluconeogenesis because of AMPK inhibition)
May also increase muscle glucose uptake Causes some weight loss, no hypoglcemia, lowers TGs NO ACTIONS ON INSULIN Can rarely cause fatal lactic acidosis |
|
|
What is the TZD mechanism of action? (rosiglitazone)
|
PPAR-gamma agonist; upregulation of genes for insulin sensitivity and lipid metabolism
Has some liver toxicity, some CV concerns; weight gain due to edema |
|
|
What is sulfonylurea's mechanism of action?
|
Bind to ATP-dependent K+ channel, inhibiting the outflux of K+, which makes the cell more excitable; because of depolarization, more facile release of insulin
Increase insulin production and release from the pancreas Can exacerbate hypoglycemia and lead to weight gain |
|
|
Describe incretin mechanism of action (exenatide)
|
Bind to gut receptors, stimulate insulin secretion, inhibit glucagon secretion, slow gastric emptying, inhibit appetite
Can lead to weight loss! Cause nausea, must be injected |
|
|
Describe the mechanism of alpha-glucosidase inhibitors (acarbose)
|
Prevent / delay the absorption of sugar in the gut, decreasing post-prandial hyperglycemia
Causes diarrhea, intestinal gas |
|
|
How does exercise reduce blood glucose in diabetic patients?
|
Exercise increases non-insulin dependent glucose transport
Raises basal metabolism, making the body more resistant to hyperglycemia Improves hypertension control |
|
|
What are the effects of insulin?
|
Decreased gluconeogenesis
Increased peripheral glucose uptake Increase glycogen synthesis Increased fatty acid synthesis Decreased proteinolysis Decreased lipolysis Insulin is the "hormone of plenty"; leads to storage of energy and retention of muscle |
|
|
What does the serum C-peptide test tell you?
|
If the pancreas is making any insulin; C-peptide is cleaved from pro-insulin and is released into the blood; only shows no insulin production
|
|
|
What does positive anti-GAD mean?
|
Existence of antibodies against glutamic acid decarboxylase; present in 85-90% of type I cases
|
|
|
Insulin glargine. Short or long acting?
|
Long acting (Lantus)
Given to mimic basal insulin secretion |
|
|
Insulin lispro. Short or long acting?
|
Short acting (Humalog)
Given before means to cover the post-prandial glucose spike |
|
|
What regulates insulin secretion?
|
Blood glucose levels
Somatostatin inhibits insulin secretion |
|
|
Glucagon: Six questions.
|
Produced in alpha cells
Peptide Free in blood Causes gluconeogenesis, release of glycogen Increased by: plasma glucose, high catacholamines, high plasma amino acids Decreased by: Somatostatin, insulin |
|
|
What is insulin resistance and what causes it?
|
Insulin resistance occurs when normal insulin levels do not trigger glucose absorption by muscle and adipose cells
Some factors implicated in insulin resistance are: TNF-alpha, leptin, IL-6, adiponectin (low levels), high NEFFAs, and central adiposy (visceral fat) |
|
|
Describe adiponectin and its potential role in insulin sensitivity
|
Adiponectin is produced by adipocytes; low levels lead to insulin resistance
Antiinflammatory and antiatherogenic properties may be related to its ability to stimulate production of NO in vascular endothelium, decreasing vascular tone |
|
|
Describe the cascade that leads to glucose uptake upon insulin stimulation
|
Insulin binds to its tyrosine kinase receptor.
Conformational change, autophosphorylate, activates kinase activity, phos'ing IRS-1 IRS-1 binds to PI3K or CBL The PI3K cascade leads to shuttling of GLUT4 to the plasma membrane, leading to uptake of glucose Insulin receptor is then taken into the cell (downregulated) |
|
|
What is the first sign of kidney damage in diabetes?
|
Protein in the urine
|
|
|
What defines Metabolic Syndrome?
|
Hypertension
Dyslipidemia Obesity Insulin Resistance usually precedes Type II diabetes |
|
|
What are symptoms of hypoglycemia? Hyperglycemia?
|
Hypo: aberrant behavior, seizures, unconsciousness, death
Hyper: Diuresis, hypotension, shock |
|
|
What are the microvascular complications of diabetes?
|
Retinopathy
Nephropathy Neuropathy |
|
|
What are the macrovascular complications of diabetes?
|
Cardiovascular disease
Cerebrovascular disease PVD |
|
|
Describe the steps required for insulin secretion from the beta cells
|
Glucose enters beta cells through GLUT2
Glucose enters glucolysis, producing ATP Once ATP reaches threshold, K+ channels close, leading to depolarization Once depolarized, voltage gated Ca+ channels open and Ca2+ enters cell Ca2+ activates phospholipase C, which cleaves PIP2 to produce IP3 and DAG IP3 binds ER, releases more Ca2+ High Ca2+ levels lead to migration of vesicles containing insulin to the plasma membrane and exocytosis |
