Beta-cell dysfunction

Chronic overwork eventually leads to beta cell dysfunction, and insulin secretion becomes inadequate to maintain blood glucose with development of symptoms. 

Giannoukakis, N., Mi, Z., Rudert, W.A., Gambotto, A., Trucco, M. and Robbins, P. (2001) Prevention of beta cell dysfunction and apoptosis activation in human islets by adenoviral gene transfer of the insulin-like growth factor I. Gene Ther., 7, 2015-2022. 

Del Prato S, Marchetti P. Targeting insulin resistance and beta-cell dysfunction the role of thiazolidine-diones. Diabetes Technol Ther. 2004 6 719-731. 

Kaneto, H., Kajimoto, Y., Fujitani, Y., Matsuoka, T., Sakamoto, K., Matsuhisa, M., Yamasaki, Y., and Hori, M. 1999. Oxidative stress induces p21 expression in pancreatic islet cell Possible implication in beta-cell dysfunction. Diabetologia 42, 1093-1097. 

Inoguchi, T., and H. Nawata. 2005. NAD(P)H oxidase activation a potential target mechanism for diabetic vascular complications, progressive beta-cell dysfunction and metabolic syndrome. Curr. Drug Targets. 6 495-501. 

Leahy JL. Natural history of beta-cell dysfunction in NIDDM. Diabetes Care 1990 i3 992-1010. 

So far the focus on the 1997 ADA and 1999 WHO revision of the diagnostic criteria has been on the impact of the revised diagnostic thresholds. Another often neglected but equally (or even more) important revision relates to the classification of patients. In 1985, patients were classified as having insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes based on the underlying disease, that is, whether beta-cell dysfunction was reduced to a level where insulin was needed to survive without entering ketoacidosis (insulin-dependent diabetes) or whether the patient had diabetes based on insulin resistance (with or without associated beta-cell dysfunction) where the patient would survive without insulin, but where insulin could be necessary to maintain acceptable metabolic... 

Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA. Beta-cell dysfunction and glucose intolerance results from the San Antonio metabolism (SAM) study. Diabetologia 2004 47(1) 31-39. 

WaUander M, Bartnik M, Efendic S et al. Beta cell dysfunction in patients with acute myocardial infarction but without previously known type 2 diabetes a report from the GAMI study. Diabetologia 2005 48( 11) 2229-2235. 

Ehses JA, Meier DT, Wueest S, et al. Toll-like receptor 2-deficient mice are protected from insulin resistance and beta cell dysfunction induced by a high-fat diet. Diabetologia. 2010 53(8) 1795—1806. 

Zhang CY, Parton LE, Ye CP, Krauss S, Shen R, Lin CT, Porco JA Jr, Lowell BB (2006) Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucose-induced beta cell dysfunction in isolated pancreatic islets. Cell Metab 3 417-427... 

The answer is A. Recent research has revealed that excess visceral fat deposits secrete several factors that have direct effects on the brain as well as directly on muscle to produce peripheral insulin resistance. Some of these newly identified factors are leptin, re-sistin, and adiponectin, whose mechanisms of action are still under active investigation. Death of pancreatic beta cells is a hallmark feature of type 1 diabetes and may occur only in very advanced stages of type 2 diabetes. Excess adipose in the thighs and buttocks does not contribute as strongly to insulin resistance as does visceral fat, presumably due to a lower level of endocrine activity of such fat depots. Dysfunction of liver lipid metabolism is more a consequence of excess activity of adipose than a cause of insulin resistance. A sedentary lifestyle contributes to build-up of excess fat stores but does not act directly to induce insulin resistance. 

Bazzi C, Petrini C, Rizza V, Arrigo G, Napodano P, PapareUa M, D Amico G. (2002) Urinary N-acetyl-beta-glucosaminidase excretion is a marker of tubular cell dysfunction and a predictor of outcome in primary glomerulonephritis. Nephrol Dial Transplant. 17 1890-1896. 

Cadmium is effectively accumulated in the kidneys. When the cadmium concentration exceeds 200 gg/g in the kidney cortex, tubular damage will occur in 10% of the population, and proteins begin to leak into urine (proteinuria). When the concentration of cadmium in the kidney cortex exceeds 300 pg/g, the effect is seen in 50% of the exposed population. Typically, excretion of low-molecular weight proteins, such as beta-microglobulin, is increased, due to dysfunction of proximal tubular cells of the kidney. The existence of albumin or other high-molecular weight proteins in the urine indicates that a glomerular injury has also taken place. The excretion of protein-bound cadmium will also be increased. 

Golden RN, Morris JE, Sack DA Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 23 181-185, 1988 Goldenberg G, Lang W, Podreka 1, et al Are cognitive deficits in Parkinson s disease caused by frontal lobe dysfunction Journal of Psychophysiology 4 137-144, 1990 Goldgaber D, Harris HW, Hla T Interleukin-1 regulates synthesis of amyloid beta-protein precursor mRNA in human endothelial cells. Proc Natl Acad Sci U S A 86 7606-7610, 1989... 

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