Diabetes Mellitus Flashcards
what is the function of PP (pancreatic polypeptide) cells?
secrete pancreatic polypeptide - stimulates secretion of gastric/intestinal enzymes, inhibits intestinal motility
fill in the blank regarding insulin release:
1. glucose uptake into beta cells is facilitated via _____
2. metabolism of glucose generates ATP, which leads to influx of ___
3. influx stimulates secretion of insulin from _____
- glucose uptake into beta cells is facilitated via GLUT2 (insulin independent)
- metabolism of glucose generates ATP, which leads to influx of Ca2+
- influx stimulates secretion of insulin from beta-cell granules
name 2 important incretins and where do they bind?
incretins: bind GPCR on beta cells, promoting insulin secretion and delaying gastric emptying (promoting satiety)
- GIP: glucose-dependent insulinotropic polypeptide
- GLP-1: glucagon-like peptide
what is the leading cause of adult-onset blindness and non traumatic lower-extremity amputations in the US?
diabetes mellitus - leading cause of ESRD (end stage renal disease), adult-onset blindness, and non traumatic lower-extremity amputations (resulting from atherosclerosis)
how long does it take for type 1 diabetes to clinically manifest?
type 1 diabetes is type IV hypersensitivity reaction that has sudden clinical onset, but results from chronic autoimmune attack years before disease is evident
classic manifestations (such as DKA) occur late in course, after 90%+ beta cells have been destroyed
which MHC genes are associated with type 1 diabetes?
HLA-DR3 and HLA-DR4
(these are class II MHC genes)
against what beta cell antigens are type 1 diabetes autoantibodies directed? (2)
- anti-insulin
- anti-glutamic acid decarboxylase (beta cell enzyme)
which type of diabetes has a stronger genetic association?
type 2 diabetes - combination of insulin resistance and inadequate insulin secretion
fill in the blank: in type 2 diabetes, insulin resistance causes a failure to inhibit _________, leading to excess circulating free fatty acids (FFAs)
hormone sensitive lipase in adipose tissue
results in excessive FA oxidation and ketone production
what is meant by “metabolic syndrome”?
metabolic syndrome - clinical findings dominated by visceral obesity, including insulin resistance, glucose intolerance, and CV risk factors (such as HTN, abnormal lipid profiles)
pancreatogenic diabetes
hyperglycemia occurring as a result of a disorder of the exocrine pancreas
underlying causes range from cystic fibrosis, chronic pancreatitis, pancreatic adenocarcinoma, etc
polyphagia + weight loss should raise suspicion for…
diabetes
classic triad is polyuria (osmotic diuresis of glucose), polydipsia, and polyphagia (negative energy balance due to catabolism of proteins, fats)
how does hyperosmolar nonketotic coma develop?
occurs in decompensated state of type 2 diabetes
triggered by severe dehydration due to polyuria caused by diabetes and inability to maintain water intake (affected individual usually older, disabled by stroke or infection)
where do AGEs (advanced glycation end products) bind and what is the effect of this interaction?
AGEs bind RAGE receptors expressed on inflammatory cells (macrophages, T cells), endothelium, and vascular smooth muscle
—> deposition of excess basement membrane material, ROS generation, proliferation of vascular smooth muscle cells and ETC matrix
what cofactor is required for glucose —> sorbitol metabolism, and what is the consequence of this for diabetic patients?
polyol pathway requires NADPH, which is also required for glutathione synthesis
significance is that in patients with diabetes who have a lot of polyol pathway activity, NADPH is depleted for glutathione synthesis, leading to susceptibility to oxidative stress —> diabetic neuropathy
