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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The subcellular localization of the incorporation of 2-(3H)-myoinositol into lipids has been studied in isolated pancreatic islets of the rat. The recovery of lipid-bound myoinositol increased with time in the nuclear, mitochondrial, microsomal, and secretory granule fractions. The utilization of a filtration technique for the more complete separation of mitochondrial and secretory granule elements permitted us to show that the recovery of lipid-bound 2-(3H)-myoinositol increased most rapidly in the secretory granule fraction. A 30-minute exposure of prelabeled islets to a stimulatory concentration of D-glucose (3.0 mg./ml.) resulted in a statistically significant decrease in the amount of lipid-bound 2-(3H)-myoinositol that was recovered from the secretory granule fraction (p less than 0.001). In contrast, exposure of islets to the elevated glucose concentration had no statistically significant effect on the recovery of lipid-bound radioactivity from other subcellular fractions. Since the majority of lipid-bound radioactivity associated with the secretory granule fraction could be recovered with the presumptive secretory granule membranes, these data suggest that the hydrolysis of phosphatidylinositol that accompanies glucose-induced insulin secretion from the rat pancreatic islet may be localized to the beta granule and, in particular, to its limiting membrane.
Diabetes 1977 Dec
PMID:Subcellular localization of the alterations in phosphatidylinositol metabolism following glucose-induced insulin release from rat pancreatic islets. 33 3

Maturity-onset diabetic patients usually have raised overnight-fasting plasma glucose levels associated with "normal" basal plasma insulin levels. The basal hyperglycemia is proportional to the degree of insulin deficiency. Basal insulin or C-peptide levels become subnormal if normal fasting plasma glucose levels are attained with insulin. Basal hyperglycemia is probably a compensatory response to maintain near-normal basal insulin levels. A logical therapy of maturity-onset diabetes is to produce basal normoglycemia by means of a constant basal insulin supplement, which can be provided by ultralente insulin. The reduced insulin response of diabetics to intravenous glucose is slightly increased when basal normoglycemia is established, suggesting that the high plasma glucose levels compromise beta cell function. The insulin response to meals in a mild diabetic is not affected by mild hyperglycemia but can be depleted if gross hyperglycemia occurs. Maintenance of normoglycemia then allows beta cell "recovery". In mild diabetics (c. less than 9 mmol per liter basal plasma glucose), chlorpropamide sufficiently stimulates beta cell secretion so that basal normoglycemia can be produced. The C-peptide response to meals is improved, whereas comparable reduction of the plasma glucose with insulin does not alter the meal response. Thus basal normoglycemia can be produced by "resting" beta cells with a basal insulin supplement or by stimulating them with sulfonylurea therapy.
Diabetes 1978
PMID:betacell function during insulin or chlorpropamide treatment of maturity-onset diabetes mellitus. 34 15

Mutation diabetes in the mouse occurs in the C57BL/Ks strain. All homozygous animals (db/db) develop obesity, elevated blood sugar levels and increased or normal blood insulin concentration. The defects in cellular immunity in db/db mice and their littermate controls were examined both in vivo and in vitro. Significant suppression of delayed footpad swelling and first and second set skin allograft rejection time were observed. In addition, DNA synthesis in spleen cells after nonspecific mitogen stimulation was markedly inhibited. Diabetic animals with a mean blood sugar of 512 +/- 101 mg/100 ml did not respond to exogenous insulin therapy by lowering their blood sugar levels or reversing the defect in DNA synthesis. Adding insulin to spleen cell culture in vitro had no demonstrable effect on their response to mitogens. Thus, mutation diabetic mice with their known defect in the peripheral utilization of insulin have markedly suppressed cell-mediated immune mechanisms.
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PMID:Impairment of cell-mediated immunity in mutation diabetic mice (db/db). 34 1

We have considered the evidence, first, that the presence of glucagon is essential in the pathogenesis of the full syndrome that results from complete insulin deficiency; second, that in the diabetic in whom insulin levels are relatively fixed, a rise in glucagon concentration contributes to endogenous hyperglycemia; and, third, that conventional methods of treatment of diabetes do not fully correct either the abnormal glucagon levels or the hyperglycemia, but when insulin therapy is supplemented with somatostatin, an agent which suppresses both glucagon and growth hormone, both hyperglycemia and hyperglucagonemia are corrected. These facts may one day provide a rationale for therapeutic efforts to suppress excess glucagon secretion in the management of diabetes in man.
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PMID:Glucagon and diabetes. 35 37

The current controversy concerning the role of glucagon in the pathogenesis of diabetes is reviewed. The traditional "unihormonal abnormality concept," namely, that all of the metabolic derangements of diabetes are the direct consequence of deficient insulin secretion or activity, and the newer so-called bihormonal abnormality hypothesis, proposing that the fullblown diabetic syndrome requires, in addition to the insulin abnormality, a relative glucagon excess, are scrutinized. The relationship of insulin deficiency to the A-cell malfunction of diabetes, the conflicting evidence concerning the essential role of glucagon in mediating the marked overproduction of glucose and ketones in severe insulin deficiency and the contribution of glucagon to the endogenous hyperglycemia of diabetics without insulin deficiency are examined. Finally, the possibility that therapeutic suppression of diabetic hyperglucagonemia may make possible better control of hyperglycemia than is presently attainable by conventional therapeutic methods is considered. It is concluded that (1) although insulin lowers glucagon levels, restoration to normal of the A-cell dysfunction of diabetes requires that plasma insulin levels vary appropriately with glycemic change; (2) that glucagon mediates the severe endogenous hyperglycemia and hyperketonemia observed in the absence of insulin; (3) that in diabetics in whom insulin is present but relatively fixed an increase in glucagon causes hyperglycemia and glycosuria; and (4) that glucagon suppression could be a potentially useful adjunct to conventional antihyperglycemic treatment of diabetics.
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PMID:Role of glucagon in the pathogenesis of diabetes: the status of the controversy. 36 7

Plasma glucagon response to glucose in diabetic subjects was observed before and after treatment. In normal subjects, plasma glucagon concentrations decreased substantially after an oral glucose load. In all diabetic patients before treatment, plasma glucagon was not suppressed and rather tended to rise paradoxically despite pronounced hyperglycemia. In diabetics treated with sulfonylurea or insulin, basal plasma glucagon concentrations were significantly lower than those in patients who were not treated. However, plasma glucagon response to an oral glucose load was not normalized by successful treatment with sulfonylurea or insulin, in spite of improvement of glucose tolerance. These results suggest that the insensitivity of the A-cell to hyperglycemia exists after treatment, and this abnormal plasma glucagon response to glucose after treatment may be caused either by impaired response of endogenous insulin to glucose, which is sustained even after treatment, or by an intrinsic defect of the A-cell.
Diabetes 1978 Dec
PMID:Failre of suppress plasma glucagon concentrations by orally administered glucose in diabetic patients after treatment. 36 90

Reversal of insulinopenia, hyperglycemia, glycosuria, and polyuria associated with severe alloxan diabetes in the rat was accomplished by syngeneic transplantation of whole late-gestation fetal rat pancreata. Intravenous glucose tolerance test (GTT) revealed an improved yet still abnormal glucose and insulin response in reversed recipients reconstituted with as few as two pancreata from fetal donors. Eight fetal donors were sufficient to return glucose and insulin response following GTT to normal. Seventy to eighty percent fewer donors were required when the pancreata were transplanted in their entirely as opposed to transplantation of pancreata subjected to prior enzymatic and mechanical dissociation. The facility and simplicity of the whole fetal pancreas implantation technique makes it an appealing model for further study of islet growth and differentiation at the transplant site and of its effect on the metabolic state of the recipient.
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PMID:Syngeneic transplantation of the fetal rat pancreas IV. Dissociated versus whole organ implantation. 36 9

Segmental pancreatic allotransplants were performed intraperitoneally in pigs with and without ligation of the duct. Exocrine pancreatic function was suppressed by the administration of glucagon. All recipients also received high doses of methylprednisolone for the first 10 days after transplant as well as cyclophosphamide until death or sacrifice. Some animals received antilymphocyte globulin (ALG) in addition. Diabetes was induced by total panreatectomy. Allotransplantation in pancreatectomized animals was successful in preventing hyperglycemia for up to 33 days of observation. ALG in the dosage used did not show any beneficial effects and varying degrees of rejection occurred in the majority of these unmatched animal pairs. Grafts without ligation of the duct seemed to show the best preservation of tissue because of absence of obstructive damage following duct ligation. Of significance is the fact that no intraperitoneal inflammatory or infectious complications occurred in recipients of either duct-ligated or unligated grafts, presumably because of suppression of exocrine function with glucagon and the reabsorptive capability of the peritoneal surface. We speculate that this is a satisfactory physiological model for continued trials in pancreatic transplantation, although antirejection therapy was far from satisfactory.
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PMID:Segmental pancreatic transplantation in pigs. 36 12

There seems little doubt that the disposal of a glucose load is progressively impaired during aging. The mechanism(s) for this alteration remains unclear. Five possibilities have been raised: (1) poor diet, (2) physical inactivity, (3) decreased lean body mass in which to store the carbohydrate load, (4) decreased insulin secretion, and (5) insulin antagonism. Although poor diet and physical inactivity may contribute to some of the abnormal glucose tolerance tests of the older population, these two factors do not provide a full explanation. Diminished lean body mass may play some role but there is almost certainly an additional effect due to aging. A few papers have suggested that glucose-induced insulin secretion may be impaired as the population ages, but the bulk of studies in this area conclude that normal or increased amounts of insulin are released by the pancreatic beta-cell during aging. If abnormalities of insulin secretion exist, either in degree or timing, they are subtle and would not seem sufficient to account for the great number of older subjects who manifest impaired glucose tolerance. The evidence for insulin antagonism seems the strongest but the data are certainly not conclusive. In actuality, the aging effect on carbohydrate metabolism may be heterogeneous in nature. Either some or all of these five factors may contribute to the aging effect to varying degrees in individual subjects. Alternatively, the glucose intolerance of aging may represent a heterogeneous group of disorders. In any event, until better methods to identify possible subgroups of these subjects and/or a marker for diabetes mellitus independent of glucose concentration become available, this problem will remain difficult to resolve. Based on the currently available data, it seems prudent to diagnose diabetes mellitus only if fasting hyperglycemia is present.
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PMID:The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly. 37 5

Behavior, pancreatic islets morphology and plasma glucose levels of male mice exposed for 2, 4, 24 and 48 hours to crowding stress were investigated. The crowding induced an intense turmoil state associated with enhanced irritability and aggressiveness among the specimens of all experimental groups. Violent fights occurred especially in the first 4--6 hours, generally with the death of 1--2 individuals from each group. The changes recorded in the pancreatic islets affected first (2 hours) exclusively the insulin-producing cells, and in subsequent intervals they progressively expanded over all cell types. The changes occurred during the experiment in all islet cell types; however the B-cells showed by far the most pronounced alterations irrespective of the studied time interval. Most changes suggested the stimulation of the entire gland secretory activity, but particularly of B-cells, which was also proved by low glycemia values recorded at 3 of the 4 crowding time intervals. On the other hand, some alterations, occurring first at 24 hours, were regarded as signs of a moderate B-cells secretory hypoactivity; they may partly support the slight hyperglycemia obtained at this time interval. The significance of the above short-term observations in the induction of glycoregulation disturbances, diabetes included, as well as the presumably mediation role of adrenal-cortex and -medulla hormones under stress conditions are discussed and correlated with findings reported in literature.
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PMID:The effects of short-term exposure to crowding stress on the pancreatic islets morphology and glycemia in mice. 38 92


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