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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyloidosis is the name given to a group of clinically protean diseases whose common feature is the tissue accumulation of amyloid fibrils which have specific optical and staining properties, and are both insoluble in physiological solvents and resistant to proteolytic enzymes. Fibril deposition and progressive extracellular infiltration eventually result in atrophy due to compression. The structure of these fibrils embraces a wide range: immunoglobulin light chain or their fragments, acute phase proteins, hormones, protease inhibitors, beta 2-microglobulin, natriuretic peptides, and proteins whose function is still unknown. Despite this heterogeneity, however, they share a common crystallographic beta-pleated sheet structure. The clinical spectrum includes apparently primary forms, amyloidosis of myeloma, forms secondary to familial Mediterranean fever, Alzheimer's disease, forms associated with type 2 diabetes or medullary carcinoma of the thyroid, inherited-familial amyloidosis, and other less common conditions. Two pathogenetic phases are involved: enhanced production of precursor proteins and their abnormal enzyme cleavage, resulting in the formation of intermediate products corresponding to the amyloid fibrils. The results of treatment are still disappointing: alkylating agents and/or cortico-steroids are used in primary forms and for amyloidosis of myeloma; colchicine in familial Mediterranean fever; DMSO in renal amyloidosis; plasmapheresis in inherited-familial forms, together with the supportive management obviously dictated by clinical manifestations.
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PMID:Amyloidosis: clinical picture, immunological and biomolecular features, treatment prospects. 174 46

The nomenclature of human diabetes mellitus (DM) has been revised, and this classification has been accepted throughout the medical world and literature. The major categories of diabetes are: insulin-dependent DM, type I or IDDM; noninsulin-dependent DM, type II or NIDDM; secondary DM or type S; impaired glucose tolerance, IGT; gestational diabetes; and previous abnormality of glucose tolerance, PrevAGT. A review of the literature has shown that over half of the documented diabetic dogs, with a single medical diagnosis, appear to be type I, IDDM, with a substantial proportion being type S, and the remainder being type II, NIDDM. Obesity is frequently associated with IGT and NIDDM. Diabetic cats most commonly have pancreatic islet destruction associated with pancreatic amyloidosis; they are insulin deficient, IDDM. The commonest causes of secondary diabetes in dogs are pancreatic damage, hyperadrenocorticism and hypersomatotropism secondary to persistent progesterone influence. Progestogen therapy is the most frequently reported cause of secondary diabetes in cats. Diabetes in horses is type S, usually secondary to a functional pituitary tumor but occasionally following chronic pancreatitis. The blood glucose ranges for normal, IGT and diabetic animals, and the normal serum insulin values of various species is tabulated.
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PMID:Definition of diabetes mellitus. 351 69

The present review draws attention to the diversity of islet lesions seen in human type 1 and type 2 diabetes. This heterogeneity of islet changes is best demonstrated by immunocytochemistry. In type 1 diabetes the endocrine pancreas is characterized by selective loss of B cells, which most likely results from a slowly acting autoimmune process depending on the presence of both genetic and environmental factors. The process starts years before overt diabetes develops and manifests when the B-cell volume is reduced by about 80%. In type 2 diabetes B cells are always present, regardless of the duration and severity of the disease, but lack any signs of functional activity. This reflects a secretory defect of the B cells which obviously becomes evident under the conditions of obesity, hyperinsulinism and insulin resistance. Obese but non-diabetic subjects show, in parallel to their hyperinsulinism, an increased B cell volume, suggesting that under prediabetic conditions the B cells have still the capacity to respond to increased functional demands by enhanced proliferation. In manifest diabetes the B cells have lost their proliferative potential. Whether this is due to an inherent defect or the consequence of a functional disturbance, is not clear. The development of islet amyloidosis most likely represents an associated functional abnormality of the B cell.
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PMID:Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited. 2471 75

Extracellular deposition of amyloid fibrils is responsible for the pathology in the systemic amyloidoses and probably also in Alzheimer disease [Haass, C. & Selkoe, D. J. (1993) Cell 75, 1039-1042] and type II diabetes mellitus [Lorenzo, A., Razzaboni, B., Weir, G. C. & Yankner, B. A. (1994) Nature (London) 368, 756-760]. The fibrils themselves are relatively resistant to proteolysis in vitro but amyloid deposits do regress in vivo, usually with clinical benefit, if new amyloid fibril formation can be halted. Serum amyloid P component (SAP) binds to all types of amyloid fibrils and is a universal constituent of amyloid deposits, including the plaques, amorphous amyloid beta protein deposits and neurofibrillary tangles of Alzheimer disease [Coria, F., Castano, E., Prelli, F., Larrondo-Lillo, M., van Duinen, S., Shelanski, M. L. & Frangione, B. (1988) Lab. Invest. 58, 454-458; Duong, T., Pommier, E. C. & Scheibel, A. B. (1989) Acta Neuropathol. 78, 429-437]. Here we show that SAP prevents proteolysis of the amyloid fibrils of Alzheimer disease, of systemic amyloid A amyloidosis and of systemic monoclonal light chain amyloidosis and may thereby contribute to their persistence in vivo. SAP is not an enzyme inhibitor and is protective only when bound to the fibrils. Interference with binding of SAP to amyloid fibrils in vivo is thus an attractive therapeutic objective, achievement of which should promote regression of the deposits.
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PMID:Serum amyloid P component prevents proteolysis of the amyloid fibrils of Alzheimer disease and systemic amyloidosis. 775 1

Amyloidosis is a heterogeneous group of disorders characterized by extracellular deposition of abnormal protein fibrils which are derived from different proteins in different forms of the disease. Asymptomatic amyloid deposition in a variety of tissues is a universal accompaniment of ageing, and clinical amyloidosis is not rare. Intracerebral and cerebrovascular beta-protein amyloid deposits are a hallmark of the pathology of both sporadic and familial Alzheimer's disease, beta 2-microglobulin-derived amyloid is a common complication of long term haemodialysis, and islet amyloid polypeptide is the fibril protein in the universal islet amyloidosis of type II diabetes mellitus. New fibril proteins have lately been identified in hereditary amyloidosis, including variants of gelsolin, apolipoprotein AI, lysozyme and fibrinogen. The development of radiolabelled serum amyloid P component (SAP) scintigraphy has allowed amyloid to be diagnosed non-invasively in vivo for the first time, provided unique insight into the distribution and size of amyloid deposits, and yielded novel information on the natural history and the effects of treatment. Amyloid deposits are in a state of dynamic turnover and can regress if new fibril formation is halted. The recent elucidation of the three dimensional structure of human SAP may enable the design of specific therapeutic agents.
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PMID:Amyloidosis. 786 80

NIDDM is a heterogeneous disease and subgroups of NIDDM include MODY (Maturity Onset Diabetes of the Young), Malnutrition-related diabetes (MRDM) and Fibrocalculus pancreatic diabetes (FCPD). Endocrine cell population is relatively unchanged in NIDDM: B-cells are reduced by up to 30% and A-cells increased by 10%. Islet amyloid is found in 96% of subjects occupying up to 80% of the islet associated with a reduction in B-cells. Amyloid formation is unlikely to cause diabetes but progressive accumulation increases the severity of the disease. Islet amyloid is formed from the islet amyloid polypeptide (IAPP), a normal constituent of B-cells, co-secreted with insulin. The causal factors for IAPP fibrillogenesis are unknown but abnormal synthesis or overproduction could be involved: stimulation of B-cell secretion in NIDDM by obesity, hyperglycaemia or suphonylurea therapy may promote amyloidosis and further aggravate islet pathology. A mutation of the glucokinase gene in MODY leads to diminished B-cell secretion but not amyloid formation. Diabetes and mutations of mitochondrial DNA is associated with poorly developed islet structure. Exocrine pancreatic size is reduced and there is evidence of sub-clinical chronic pancreatitis in NIDDM. In MRDM and FCPD, chronic pancreatitis and exocrine necrosis is associated with reduced insulin secretion. Unlike cystic fibrosis where islet amyloid is present in diabetic individuals, amyloid is absent from subjects with FCPD. Pathological changes in the exocrine and endocrine pancreas in NIDDM results from and contributes to the pathophysiology of insulin secretion in NIDDM.
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PMID:Pancreatic pathology in non-insulin dependent diabetes (NIDDM). 852 18

Islet amyloid polypeptide (IAPP), 'amylin', is the component peptide of islet amyloid formed in Type 2 diabetes. IAPP is expressed in islet beta-cells and is derived from a larger precursor, proIAPP, by proteolysis. An in vitro translation/translocation system was used to separately examine processing of human proIAPP by the beta-cell endopeptidases PC2, PC3 or furin. ProIAPP was converted to mature IAPP by PC2 but there was little conversion by furin or PC3. These data are consistent with processing of proIAPP in beta-cell secretory granules. Abnormal cellular proteolysis associated with type 2 diabetes could contribute to IAPP amyloidosis.
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PMID:Processing of pro-islet amyloid polypeptide (proIAPP) by the prohormone convertase PC2. 855 6

Six 15- to 20-year-old obese cynomolgus monkeys were determined to have diabetes mellitus. These monkeys were hyperglycemic and hypertriglyceridemic, yet remained nonketotic for several years before requiring clinical intervention. A significant decrease in glucose disappearance and an increased area under the glucose disappearance curve were found in response to intravenous glucose tolerance testing. Basal hyperinsulinemia was found in three animals that, in response to glucose stimulation, had a blunted insulin response, resulting in an overall decrease in the area under the insulin curve. Two animals died during the study and had extensive amyloid infiltration of pancreatic islets. The combined findings of old age, obesity, hyperinsulinemia, improvement in response to caloric restriction, and islet amyloidosis are consistent with type 2 diabetes mellitus.
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PMID:Diabetes mellitus and islet amyloidosis in cynomolgus monkeys. 869 17

A high proportion of patients with cystic fibrosis (CF) develop diabetes mellitus. In common with type II diabetes mellitus, diabetes mellitus in CF is characterized by a progressive decline in beta-cell function and an approximately 50% decline in beta-cell mass. It is not known whether islet amyloidosis (characteristic of type II diabetes mellitus) is present in diabetes mellitus complicating CF. To address this, pancreatic samples were obtained at autopsy from 9 control cases (without CF) and 41 cases of CF that were, in turn, subdivided into 13 nondiabetic, 12 borderline diabetic, and 16 diabetic cases based on clinical criteria. Islet amyloid was detected by light microscopy in 69% cases of CF with diabetes mellitus, 17% of cases with borderline diabetes mellitus, and none of the nondiabetic cases. Islet amyloid was not present in any of the control cases. Islet amyloidosis derived from islet amyloid polypeptide is a characteristic feature of diabetes mellitus in CF as well as type II diabetes mellitus.
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PMID:Diabetes mellitus in cystic fibrosis is characterized by islet amyloidosis. 877 10

Amyloid deposition is associated with a diverse range of disorders that includes Alzheimer's disease, type II diabetes mellitus and dialysis arthropathy. Although less common, systemic AA and AL amyloidosis remain important because effective treatments have increasingly become available. The pathology in all forms of amyloidosis involves the extracellular deposition of protein as characteristic fibrillar aggregates which interfere with tissue structure and function. Amyloid fibrils are derived from different unrelated proteins in the different forms of the disease but share many common properties, including the capacity to bind the normal plasma protein serum amyloid P component (SAP). This is the basis for our development of radiolabelled SAP as a nuclear medicine tracer for the diagnosis and quantitative monitoring of amyloid. Serial studies have shown that the deposits are far from inert but are actually turned over quite rapidly in many patients. The treatment of amyloidosis involves supportive measures whilst every effort is made to reduce the supply of the respective fibril precursor protein. Under favourable circumstances further amyloid deposition will be prevented. existing deposits will regress and improvement of organ function will occur. Since this strategy is not always possible or may fail, new approaches to inhibit fibril formation and promote regression of amyloid are being pursued.
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PMID:Amyloidosis: a review of recent diagnostic and therapeutic developments. 937 34


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