Term
| Describe beta cell granules. |
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Definition
| they have rectangular crystalline matrix surrounded by a halo |
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Term
| Describe alpha cell granules. |
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Definition
| they are round with closely applied membranes and a dense center |
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Term
| Describe delta cell granules. |
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Definition
| they are large and pale with with closely applied membranes |
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Term
| What does PP cell secretion do? |
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Definition
| Stimulates secretion of gastric and intestinal enzymes, inhibits motility. |
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Term
| Describe PP cell locations in the pancreas and describe the cell granules. |
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Definition
| In islets but also scattered, they have small dark granules. |
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Term
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Definition
| Elaborate VIP, which induces glycogenolysis and hyperglycemia, stimulates GI fluid secretion and causes secretory diarrhea. |
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Term
| What do enterochromaffin cells do? They are the source of pancreatic tumors that cause which syndrome? |
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Definition
| Synthesize serotonin, carcinoid syndrome |
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Term
| What is the most important susceptibility locus for Type 1 Diabetes? What are the associated alleles? |
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Definition
| HLA on 6p21. DR3 and DR4. DR3/4 with DR8 is especially high risk. |
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Term
| What are some of the non-HLA susceptibility loci for Type 1 Diabetes? |
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Definition
| insulin (with VNTRs in promotor region), CTLA4 and PTPN22 (which normally inhibit T cell responses), CD25 (a-chain of the IL-2 receptor which is important for maintaining regulatory T cells) |
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Term
| What are the 3 proposed mechanisms for how viral infection might be involved in Type 1 Diabetes? |
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Definition
| bystander damage, molecular mimicry, viral deja vu |
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Term
| The islet auto-antigens that are the targets of immune attack in Type 1 Diabetes may include... |
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Definition
| insulin itself, glutamic acid decarboxylase (GAD), islet cell autoantigen 512 (ICA512) |
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Term
| What is the genetic factor most strongly associated with Type 2 Diabetes? |
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Definition
| transcription factor 7-like-2 (TCF7L2) on 10q, encodes TF in WNT signaling pathway |
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Term
| Loss of insulin sensitivity in which cells is likely to be that largest contributor to the pathogenesis of insulin resistance? |
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Definition
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Term
| How are NEFAs involved in insulin resistance? |
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Definition
| Excesses overwhelm FA oxidation pathways, intermediates accumulate (DAG and ceramide), they activate serine/threonine kinases, causes aberrant phosphorylation of the insulin receptor and IRS proteins. This attenuates the insulin signaling, and PEPCK can ramp up gluconeogenesis. Excess NEFAs also compete with glucose for oxidation. |
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Term
| How do leptin and adiponectin improve insulin sensitivity? |
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Definition
| They enhance the activity of AMP-activated protein kinase, which promotes FA oxidation in liver and skeletal muscle. |
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Term
| What are some of the inflammatory CKs secreted by adipose tissue, and why do they matter? |
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Definition
| IL-6, TNF, MCP-1, they increase cellular stress, which activates signaling cascades that antagonize insulin action on peripheral tissues |
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Term
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Definition
| nuclear receptor and TF in adipose tissue, promotes secretion of anti-hyperglycemic adipokines and shifts deposition of NEFAs toward adipose tissue and away from liver and skeletal muscle. |
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Term
| What condition is characterized by 1) autosomal dominant inheritance, 2) early onset of diabetes, 3) absence of obesity, 4) absence of beta cell autoantibodies? |
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Definition
| Genetic defects in beta cell function resulting in monogenic diabetes. Caused by a heterogeneous group of defects. |
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Term
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Definition
| Hemizygous LOF mutation in one of 6 genes. Glucokinase (GCK) mutation causes mild fasting hyperglycemia and 50% of carriers develop gestational diabetes. Other 5 are TFs that control insulin expression and beta cell mass (like IPF1) |
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Term
| Mutations of KCNJ11 and ABCC8 genes results in which condition? What do these genes encode? GOF mutations cause what problem? |
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Definition
| Permanent neonatal diabetes, Kir6.2 and SUR1 subunits of the ATP-sensitive K-channel on beta cells. GOF mutations cause constitutive activation and hypoinsulinemic diabetes. Severe hyperglycemia, ketoacidosis, 20% with neuro symptoms. |
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Term
| What causes maternally-inherited diabetes and deafness? |
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Definition
| mitochondrial DNA mutations, impairs ATP synthesis in beta cells, decreased insulin secretion. |
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Term
| People with insulin receptor mutations have what type of insulin resistance? What other symptom is this associated with? In females, what is often found? |
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Definition
| Type A insulin resistance, acanthosis nigricans, polycystic ovaries and increased androgen levels |
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Term
| Which rare group of genetic disorders has in common insulin resistance, diabetes, hypertriglyceridemia, acanthosis nigricans, and hepatic steatosis? |
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Definition
| Lipatrophic diabetes, which is hyperglycemia accompanied by loss of subcutaneous fat. There are multiple subtypes, with different causes. Dominant-neg mutations have been found in PPARG. |
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Term
| What is the lifetime of the RBC? |
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Definition
|
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Term
| What are AGEs? What do they bind to? On what types of cells? |
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Definition
| Advanced glycation end products, formed from glucose-derived dicarbonyl percursors interacting with amino groups of proteins. Bind to RAGE receptor on inflammatory cells, endothelium, vasc smooth muscle. |
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Term
| What is the effect on AGE-RAGE signaling on intimal macrophages? |
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Definition
| release of pro-inflammatory CKs and growth factors |
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Term
| What is the effect of AGE-RAGE signaling on endothelial cells and macrophages? |
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Definition
| increased procoagulant activity |
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Term
| What is the effect of AGE-RAGE signaling on endothelial cells? |
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Definition
|
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Term
| What is the effect of AGE-RAGE signaling on vascular smooth muscle cells and ECM? |
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Definition
| Enhanced proliferation and synthesis of ECM |
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Term
| What can AGEs do to extracellular matrix proteins? What effects does this have? |
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Definition
| cross linking, decreases elasticity, predispose to shear stress and injury, decreases endothelial cell adhesion and increases fluid extravasation, makes proteins resistant to degradation, traps nonglycated plasma or interstitial proteins |
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Term
| Intracellular hyperglycemia stimulates synthesis of DAG from glycolytic intermediates, leading to activation of which enzyme? |
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Definition
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Term
| Activation of which enzyme is responsible for these effects: production of VEGF, elevated endothelin-1, decreased NO from decreased expression of endothelial nitric oxide synthase, production of profibrogenic factors like TGF-B, production of PAI-1 leading to reduced fibrinolysis, production of proinflammatory CKs in vascular endothelium |
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Definition
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Term
| How does intracellular hyperglycemia cause increased cellular susceptibility to oxidative stress? |
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Definition
| excess glucose is metabolized by aldose reductase to sorbitol and eventually to fructuse, the reaction uses NADPH. NADPH is required by glutathione reductase to regenerate GSH. GSH is an important antioxidant. |
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Term
| Reduction in number and size of islets is seen most often in Type __ DM. ____________ infiltrates may also be found at the time of clinical presentation. |
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Definition
| 1, leukocytic (principally T cells) |
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Term
| In type 2 DM there may be a subtle ______ in islet cell mass, and deposition of _______ within islets. |
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Definition
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Term
| An increase in the number and size of islets is characteristic of... |
|
Definition
| nondiabetic newborns of diabetic mothers. |
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Term
| What is the hallmark of diabetic macrovascular disease? What distinguishes it from nondiabetics? |
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Definition
| accelerated atherosclerosis, just the severity and earlier onset |
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Term
| What is the most common cause of death in diabetics? |
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Definition
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Term
| What is the vascular lesion associated with HTN that is more prevalent and severe in diabetics? |
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Definition
| hyaline arteriolosclerosis, hyaline thickening of the wall causing narrowing of the lumen |
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Term
| What is the diffuse thickening of basement membranes in diabetics called? What are the capillaries like? |
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Definition
| Diabetic microangiopathy, caps are more leaky to plasma proteins |
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Term
| What are the 3 main types of lesions in diabetic nephropathy? |
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Definition
| glomerular lesions, renal vascular lesions, pyelonephritis |
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Term
| What are the most important glomerular lesions in diabetic nephropathy? |
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Definition
| GBM thickening, diffuse mesangial sclerosis, nodular gomerulosclerosis |
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Term
| What is diffuse mesangial sclerosis? |
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Definition
| a diffuse increase in mesangial matrix |
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Term
| Nodular glomerulosclerosis is also known as.. |
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Definition
| intercapillary glomerulosclerosis or Kimmelsteil-Wilson disease |
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Term
| Fibrin caps and capsular drops are associated with... |
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Definition
| Nodular glomerulosclerosis |
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Term
| In diabetics, hyaline arteriolosclerosis affects which arterioles of the glomerulus? |
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Definition
|
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Term
| Where does pyelonephritis usually begin? Where does it spread? What special pattern is seen more often in diabetics? |
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Definition
| interstitial tissue, to the tubules. Necrotizing papillitis. |
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Term
| Diabetic ocular complications include... |
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Definition
| cataracts, glaucoma, retinopathy |
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Term
| What are islet cell tumors called? What do they resemble? They make up what percentage of pancreatic tumors? |
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Definition
| pancreatic endocrine neoplasms, carcinoid tumors, 2% |
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Term
| What percentage of insulinomas are benign? |
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Definition
|
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Term
| What is the characteristic clinical picture of insulinomas? |
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Definition
| hypoglycemic episodes, with confusion, stupor or LOC, precipitated by fasting or exercise |
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Term
| 10% of insulinomas are... |
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Definition
|
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Term
| Describe the appearance of solitary insulinomas. |
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Definition
| Usually small, encapsulated, pale to red-brown. Look like giant islets. Usually have deposition of amyloid. |
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Term
| What are some situations that result in focal or diffuse hyperplasia of the islets? |
|
Definition
| maternal diabetes, Beckwith-Wiedemann syndrome, K-channel protein/sulfonylurea recep mutations |
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Term
| What type of tumor is found in Zollinger-Ellison syndrome? Where are they found? What are other features of this condition? |
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Definition
| gastrinomas, duodenum, peripancreatic soft tissues, pancreas. Pancreatic islet cell lesions, hypersecretion of gastric acid, severe peptic ulcers. Over half are invasive at Dx. Can be part of MEN-1, have multifocal tumors. Also have diarrhea, ulcers in unusual locations like jejunum. |
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Term
| Which condition is associated with mild DM, necrolytic migratory erythema and anemia? Who does it occur in most frequently? |
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Definition
| alpha cell tumors, glucagonomas |
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Term
| Which condition is associated with DM, cholelithiasis, steatorrhea, and hypochlorhydria? |
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Definition
| delta cell tumors, somatostatinomas |
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Term
| Which condition is associated with watery diarrhea, hypokalemia, and achlorhydria (WDKA syndrome)? What else can this be associated with? |
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Definition
| VIPoma. Neural crest cell tumors. |
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Term
| Which tumors produce serotonin? |
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Definition
| Pancreatic carcinoid tumors |
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Term
| Which pancreatic tumors are endocrinologically asymptomatic? |
|
Definition
| PP-secreting endocrine tumors |
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Term
| In addition to insulin, glucagon, SS, VIP, PP and gastrin, pancreatic endocrine tumors may produce... |
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Definition
| ACTH, MSH, ADH, serotonin and norepi. (multihormonal tumors) |
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