Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperglycemia induced in animals by beta cell toxins or by pancreatectomy can be reversed by pancreatic islet transplantation. Abnormal carbohydrate metabolism in juvenile onset human diabetics has also been corrected, albeit temporarily because of graft rejection, by pancreatic transplantation. It does not necessarily follow that naturally occurring diabetes in animals or adult onset diabetes in man would respond to similar treatment. Islet transplantation was studied in mice with chemically induced or genetically determined diabetes. Streptozotocin-induced diabetic mice were permanently cured by syngeneic islets and, when immunosuppressed, were rendered normoglycemic for six weeks after receiving xenogeneic rat islets. In contrast, histocompatible islets from normoglycemic coisogenic donors were ineffective in hyperglycemic db/db recipients as were xenogeneic rat islets in immunosuppressed db/db hosts. However, when islets were isolated from db/db donors and transplated to genetically normal coisogenic mice, which had been rendered hyperglycemic with streptozotocin, they became normoglycemic. Apparently the metabolic defect in the db/db mice, which is similar in some ways to human maturity onset diabetes, does not reside in their islets as these cells can function normally if transplanted to genetically nondiabetic hosts. In two other types of genetic diabetes (ob/ob and NZO) islet transplantation was more effective. Pancreatic transplantation is unlikely to be the proper treatment for all types of diabetes even if technical and immunological problems are overcome.
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PMID:Islet transplantation in genetically determined diabetes. 14 16

Nonketotic hyperosmolar diabetic coma is a rare manifestation of juvenile diabetes, in contrast to adult onset diabetes. To date only 20 cases have been published, the majority of them infants and toddlers. This type of diabetic coma is seen with unusual frequency in children with Down's syndrome and psychomotor retardation. The clinical picture is characterised by severe dehydration, hyperglycemia with often extremely high blood sugar levels, hyperosmolarity and glucosuria without ketonuria. Mortality in children has been high (24%). This paper reports the case of a 14-month-old girl with Down's syndrome. Clinical and therapeutic as well as pathogenetic aspects are discussed.
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PMID:[Hyperosmolar nonketotic diabetic coma in children]. 15 87

An account is given of the present conception of asymptomatic (chemical) diabetes in the pediatric age group, which also has been named MODY (maturity-onset type of diabetes of young people). Long-term studies show that about 10% will eventually decompensate to overt diabetes. In contrast to classical juvenile-onset type of diabetes the inheritance of MODY seems to be autosomal dominant in many cases. Some authors have suggested that insulin resistance exists in non-obese patients with asymptomatic diabetes, but this view is not supported by observations of the author. Obese patients should reduce their body fat, but other therapeutic approaches are difficult to evaluate because of the normal fluctuation of the disease. There is no general agreement in the literature concerning the value of insulin treatment. The author supports the view that insulin treatment should be started in the late stages of chemical diabetes just before symptomatic disease emerges. In the long run this approach may ameliorate the condition due to the preservation of some beta-cell function for long periods. An unsettled question is whether early insulin treatment in asymptomatic diabetes will delay diabetic vascular complications.
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PMID:Asymptomatic diabetes in childhood and adolescence. A review. 35 15

The idea that the gene(s) that cause diabetes mellitus can be expressed in extrapancreatic cells has been examined by tissue culture techniques. Skin biopsies were obtained from 25 normal subjects (N), 26 overt diabetics (D), 16 of juvenile onset (JOD) and 9 of maturity onset (MOD), and 21 subjects genetically predisposed to diabetes (P) on the basis of maturity-onset diabetes in both parents. Each biopsy was subdivided, multiple skin fragments were explanted in vitro, and several parameters of cellular outgrowth were monitored in primary and secondary cultures until cell division ceased because of senescence. In general, the rank order of growth vigor was N greater than P greater than D although differences were often marginal and statistically significant between N and JOD and(or) MOD. Outgrowth of epithelial cells was more vigorous in N explants in early stages, but later, JOD and MOD cells grew better than those of N. Outgrowth of fibroblast cells from N explants was more vigorous both at early and later stages and required less time to achieve maximum percent outgrowth. In secondary cultures, N cells grew faster than the other three groups so that fewer days elapsed between subcultures but significant differences were only seen between N and one or two of the other groups over some of the first seven subcultures. The onset of cellular senescence occurred earlier in P and JOD cultures both in mean population doublings and calendar time. N cultures had a higher percent surviving clones after picking than MOD, and a shorter recloning time than clones of JOD. The replicative life-spans of cultures (mean population doublings +/- SE) were N = 52.54 +/- 2.24, P = 47.84 +/- 2.43, JOD = 47.12 +/- 2.99, and MOD = 46.40 +/- 4.04, but differences did not reach significance for N vs the other three groups. The data demonstrate that cellular growth is impaired in both JOD and MOD types of cultures and to a generally lesser extent in P cultures. This is consistent with intrinsic genetic defects but the possibility that persistent deleterious effects of in vivo pathophysiology contribute alone or in combination cannot be ruled out. Therefore, the diabetic defect(s) can be expressed in extrapancreatic cells of mesenchymal origin. This system should prove useful in exploring the interplay between genetic and environmental factors in diabetes, the mechanisms(s) of hyperglycemia and other metabolic derangements, and the propensity that affected individuals have to develop degenerative diseases.
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PMID:Diabetes mellitus and genetic prediabetes. Decreased replicative capacity of cultured skin fibroblasts. 42 58

In a family with maturity-onset type of diabetes mellitus inherited as a dominant, autosomal trait (MODY), the HLA genotypes were compared with the glucose tolerance and the plasma insulin response to oral glucose. In the members with impaired glucose tolerance, the plasma insulin response was of the insulino-tardic type, while those with normal or borderline glucose tolerance had a normal plasma insulin response. HLA tissue typing for A, B, C and D series antigens carried out in 19 of the members showed no association between specific HLA antigens and imparied glucose tolerance. Moreover, when analysing the segregation of the disease and the HLA characters, several recombinants between MODY and HLA would have to be postulated if the gene(s) for this form of diabetes mellitus should be closely linked to the HLA locus.
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PMID:HLA antigens in a family with maturity-onset type diabetes mellitus. 58 Aug 33

We have used a continuous intravenous infusion of glucose (6 mg/kg/min), insulin (80 mU/min), epinephrine (6 mug/min), and propranolol (0.08 mg/min) to directly assess insulin resistance in 14 untreated adult onset diabetics with a mean (plus or minus SE) fasting plasma glucose level of 217 plus or minus 17 mg/100 ml. During the infusion endogenous insulin secretion is inhibited and steady-state plasma glucose and insulin levels are achieved after 90 min. Since similar steady-state levels of plasma insulin are achieved in all subjects, the plasma glucose concentration observed during the steady-state period is a measure of an individual's insulin resistance. Under these conditions, the mean (plus or minus SE) steady-state plasma glucose level of the 14 diabetic patients was 350 plus or minus 16 mg/100 ml, while that of 12 normal subjects was 121 plus or minus 4 mg/100 ml. Additional studies were performed in which control subjects and patients with diabetes had their fasting plasma glucose levels acutely raised or lowered to comparable levels before receiving the basic infusion mixture of glucose, insulin, epinephrine, and propranolol. The results of these studies indicated that differences in initial plasma glucose levels could not account for the different glucose responses of the two groups to the basic infusion. Finally, the mean (plus or minus SE) steady-state plasma glucose level of 104 plus or minus 17 mg/100 ml observed during the same basic infusion in five patients with fasting hyperglycemia (mean plus or minus SE, 142 plus or minus 12 mg/100 ml) secondary to chronic pancreatitis suggested that neither chronic hyperglycemia nor hypoinsulinemia per se necessarily lead to insulin resistance. These results demonstrate that marked insulin resistance exists in adult onset diabetics with fasting hyperglycemia. Since previous studies have documented the presence of insulin resistance in patients with chemical diabetes, the possibility exists that insulin resistance may be characteristic of adult onset diabetes mellitus.
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PMID:Demonstration of insulin resistance in untreated adult onset diabetic subjects with fasting hyperglycemia. 111 64

1 In 4058 diabetics, an inverse relation (negative semilogarithmic correlation) was found between the age of onset and the familial aggregation of diabetes mellitus (P less than 0.01). Hence, juvenile (especially infantile) diabetes appears to be predominantly caused by genetic defects (mutations), whereas adult onset diabetes appears to be essentially based on epigenetic factors. 2. In 3890 diabetics with an onset age of more than 10 years, a highly significant predominance of familial diabetes aggregation was observed on the maternal side as compared to the paternal side (P less than 0.001). This finding suggests the possibility of an epigenetic ("teratogenetic") mode of diabetes transmission mediated by the mother.
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PMID:On possible genetic and epigenetic modes of diabetes transmission. 124 72

We investigated a family in which at least 4 men in 3 generations had a syndrome of obesity, mild mental retardation, delayed puberty, macroorchidism, acanthosis nigricans, hyperinsulinemia, and later overt insulin-resistant diabetes mellitus (non-insulin-dependent diabetes mellitus, NIDDM). The patients have markedly curly scalp hair, deficient face and body hair. Their teeth were healthy and normal in size and position. The clinical and biochemical findings and characteristics of the insulin receptors investigated in fibroblasts are reported. There was normal insulin binding to fibroblasts in the 2 brothers and their father. However, insulin-stimulated RNA synthesis was decreased as compared to that of normal control individuals. These findings suggest a postbinding defect of insulin action. The pedigree documents an autosomal dominant mode of inheritance. The diagnosis is of practical importance since it enables medical supervision of gene carriers in a preclinical state of atherosclerotic complications and overt diabetes. The findings in this family have relevance also to the explanation of familial mild mental retardation and to the study of different forms of insulin resistance due to a disturbance in biosignal transfer.
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PMID:Autosomal dominant insulin resistance syndrome due to postbinding defect. 128 80

Diabetes mellitus is commonly associated with systolic and diastolic hypertension, and a wealth of epidemiological data suggest that this association is independent of age and obesity. Much evidence indicates that the link between diabetes and essential hypertension is hyperinsulinemia. Thus, when hypertensive patients, whether obese or of normal body weight, are compared with age- and weight-matched normotensive controls, a heightened plasma insulin response to a glucose challenge is found consistently. A state of cellular resistance to insulin action subtends the observed hyperinsulinism. Using the insulin/glucose clamp technique in combination with tracer glucose infusion and indirect calorimetry, it has been demonstrated that the insulin resistance of essential hypertension is located in peripheral tissues (muscle), is limited to nonoxidative pathways of glucose disposal (glycogen synthesis), and correlates directly with the severity of hypertension. The reasons for the association of insulin resistance and essential hypertension can be sought in at least four general types of mechanisms: sodium retention, sympathetic nervous system overactivity, disturbed membrane ion transport, and proliferation of vascular smooth-muscle cells. Physiological maneuvers, such as caloric restriction (in the overweight patient) and regular physical exercise, can improve tissue sensitivity to insulin; good evidence indicates that these maneuvers also can lower blood pressure in both normotensive and hypertensive individuals. Insulin resistance and hyperinsulinemia also are associated with an atherogenic plasma lipid profile. Elevated plasma insulin concentrations enhance very-low-density lipoprotein (VLDL) synthesis, leading to hypertriglyceridemia. Progressive elimination of lipid and apolipoproteins from the VLDL particle leads to an increased formation of intermediate density and low-density lipoproteins, both of which are atherogenic. Last, insulin per se, independent of its effects on blood pressure and plasma lipids, is known to be atherogenic. The hormone enhances cholesterol transport into arteriolar smooth-muscle cells and increases endogenous lipid synthesis by these cells. Insulin also stimulates the proliferation of arteriolar smooth-muscle cells, augments collagen synthesis in the vascular wall, increases the formation of and decreases the regression of lipid plaques, and stimulates the production of a variety of growth factors. In summary, insulin resistance appears to be a syndrome that is associated with a clustering of metabolic disorders, including type II diabetes mellitus, obesity, hypertension, lipid abnormalities, and atherosclerotic cardiovascular disease.
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PMID:Insulin resistance, hyperinsulinemia, and coronary artery disease: a complex metabolic web. 128 37

Non-insulin-dependent (type II) diabetes mellitus (NIDDM) is characterized by hyperglycaemia and insulin resistance, and affects nearly 5% of the general population. Inherited factors are important for its development, but the genes involved are unknown. We have identified a large pedigree in which NIDDM, in combination with a sensorineural hearing loss, is maternally inherited. The maternal inheritance and the observed decrease in mitochondrial enzyme activities of the respiratory chain indicate a genetic defect in the mitochondrial DNA. An A to G transition was identified at nucleotide 3,243, a conserved position in the mitochondrial gene for tRNA(Leu)(UUR). This mutation cosegregates with the disease in this family and is absent in controls, and indicates that a point mutation in mitochondrial DNA is a pathogenetic factor for NIDDM.
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PMID:Mutation in mitochondrial tRNA(Leu)(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. 128 50


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