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

A beta-variant hemoglobin, first misjudged as a marked elevation of Hb A1, was found in a 68-year-old Japanese female with diabetes mellitus. This hemoglobin was isolated by Bio-Rex 70 chromatography combined with chromatofocusing, and was found to be Hb Hope, beta 136(H14)Gly----Asp, by classical and high performance liquid chromatographic peptide mapping techniques. Intrinsic oxygen affinity of this hemoglobin was approximately one-third as compared with that of Hb A0. This property was still observed in the constituent beta subunits isolated. Effects of such allosteric effectors as H+ (at a fixed concentration of Cl-), anion (Cl-), 2,3-diphosphoglycerate and carbon dioxide were more or less depressed. Among others, a marked reduction in the carbamate effect should be noted in a structural interpretation of the functional modifications. Subunit cooperativity, on the contrary, was not different from that in Hb A0 (n = 2.8-2.9). Explanation of these altered functions were attempted on the basis of the altered structure. The reduced stability of Hb Hope is also described.
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PMID:Hb Hope, beta 136(H14)Gly----Asp, in a diabetic Japanese female and its functional characterization. 270 63

Transcutaneous measurement of oxygen pressure (PcO2) and carbon dioxide pressure (PcCO2) was performed in nine patients with histologically confirmed necrobiosis lipoidica. None of the patients had diabetes mellitus. All measurements were taken at the lower leg. In each case, the atrophic center, the inflamed border, and the surrounding clinically normal skin of necrobiosis lipoidica were examined at 44 degrees C sensor temperature (maximal vasodilatation). Statistically significant hypoxia was found in the area of necrobiosis lipoidica, which was even more pronounced in the inflamed border. Inhalation of 100% oxygen provoked a marked increase in the PcO2 in the lesion, but the values were still significantly lower than in the normal skin. At the edge of the lesions the PcCO2 was significantly elevated. These findings support a vascular origin of necrobiosis lipoidica, involving reduced vascular perfusion combined with diffusion block.
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PMID:[Transcutaneous measurement of oxygen and carbon dioxide pressure in necrobiosis lipoidica]. 273 51

Fifteen week old male Wistar rats (n = 7) were made diabetic by intravenous injection of streptozotocin (50 mg/kg). Age-matched, untreated male Wistar rats (n = 9) served as controls. Hearts were removed after 5-6 weeks of diabetes, and the isometric developed tension (T) of isolated left ventricular papillary muscles and its first derivative (dT/dt) were measured at a frequency of 0.2 Hz. During testing, the muscles were perfused with Tyrode's solution (Ca2+ concentration was half of normal Tyrode's solution, pH 7.4, 32 degrees C, bubbled with 95% O2 and 5% CO2). In addition, the left ventricular isoenzyme pattern, which is related to myocardial energetics, was determined by pyrophosphate gel electrophoresis. There was no significant difference in isometric developed tension between diabetic and control rats (DM: 2.90 +/- 0.89 vs controls: 2.87 +/- 0.85 g/mm2, mean +/- SD), but in diabetic rats, dT/dtmax decreased significantly as compared with controls (DM: 23.5 +/- 4.2 vs controls: 31.9 +/- 7.9 g/mm2.s, p less than 0.05). Myocardial mechanical responses to isoproterenol (10(-7)M) and dibutyryl cyclic AMP (10(-5)M) also decreased in diabetic rats. The left ventricular myosin isoenzyme pattern shifted toward VM-3 in diabetic rats (VM-3: DM: 74.9 +/- 10.7 vs controls: 9.5 +/- 4.1%, p less than 0.001). These results indicate that diabetes influences myocardial contractility and changes cardiac energetics. Post-receptor processes may play a role in myocardial mechanical responses to catecholamines in streptozotocin-diabetic rats.
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PMID:Myocardial mechanical and myosin isoenzyme alterations in streptozotocin-diabetic rats. 284 6

Recent studies in man demonstrated a marked ketogenic effect of increased plasma norepinephrine concentrations as observed in diabetic ketoacidosis. Since this effect may have been due either to increased substrate supply for ketogenesis (lipolysis) or to direct hepatic activation of ketogenesis, the latter mechanism was examined in isolated rat hepatocytes. Incubation of hepatocytes with norepinephrine (10(-7) to 10(-4) M) resulted in a dose-dependent increase in conversion of the long-chain fatty acid [1-14C]palmitate into ketone bodies and CO2. Norepinephrine decreased [1-14C]palmitate conversion into triglycerides without affecting fatty acid uptake. Norepinephrine enhanced ketogenesis from [1-14C]palmitate in a physiologic range of fatty acid concentrations (0.5-2.5 mM), but failed to affect fatty acid esterification to phospholipids or mono- and diglycerides. In contrast to long-chain fatty acids, oxidation of the medium-chain fatty acid [1-14C]octanoate to ketone bodies was not enhanced by norepinephrine, whereas CO2 production increased. The effect of norepinephrine on [1-14C]fatty acid oxidation was blocked by the alpha 1 receptor blocker prazosin. The results demonstrate that norepinephrine diverts long-chain fatty acids into the pathways of oxidation and ketogenesis away from esterification, suggesting enhanced carnitine-dependent mitochondrial fatty acid uptake. The studies using octanoate indicated that norepinephrine also enhanced fatty acid oxidation by increasing the flux of acetyl-CoA through the Krebs cycle. The data suggest that stress-associated sympathetic activation and norepinephrine discharge, as observed in diabetic ketoacidosis, result in direct activation of ketogenesis in the liver.
Diabetes 1985 Aug
PMID:Effect of norepinephrine on ketogenesis, fatty acid oxidation, and esterification in isolated rat hepatocytes. 286 86

To determine whether endogenous GH contributes to impairments of glucose metabolism in diabetes mellitus, we examined the metabolic consequences of GH deficiency in streptozotocin (SZ)-diabetic rats. Diabetic rats were treated with a highly specific antirat GH serum (ArGH) to neutralize the activity of circulating GH, and glucose metabolism was measured in adipose tissue in vitro in the absence or presence of insulin. Short term (6-h) GH deficiency led to a 10% decrease in hyperglycemia (P = 0.002) in SZ-diabetic rats. Basal glucose oxidation and insulin responses in adipose tissue were unchanged by acute ArGH treatment. Since hyperglycemia was improved when adipose tissue metabolism was unaltered, GH-dependent changes occurring in other tissues, such as liver or muscle, most likely contribute to derangements of glucose metabolism in diabetes, even when GH is not elevated. Prolonged GH deficiency was produced by infusing ArGH into SZ-diabetic rats for 5 days. In these animals, the relative fat content (percentage of wet weight) of adipose tissue was significantly increased. In addition, the conversion of [14C]glucose to lipid and CO2 in adipose tissue was significantly increased with chronic GH deficiency in SZ-diabetic rats, but the ability of insulin to stimulate glucose metabolism in the tissue was unaffected. These results indicate that endogenous GH suppresses basal glucose utilization in adipose tissue of diabetic animals; this is reversed by prolonged (5-day), but not acute (6-h), ArGH treatment. Taken together, these findings suggest that the role of endogenous GH in the regulation of glucose metabolism in diabetic animals involves several mechanisms and multiple tissues.
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PMID:Metabolic effects of acute and prolonged growth hormone deficiency in streptozotocin-diabetic rats. 294 75

The effect of short-term (8-10 days) optimal glycaemic control achieved by continuous subcutaneous insulin infusion on resting energy expenditure and food-induced thermogenesis was studied. Oxygen consumption and carbon dioxide production were measured by indirect calorimetry in six newly-diagnosed and six chronically-treated diabetic children before and following the consumption of a standardized test meal. The metabolic and hormonal responses to the test meal and nutrient utilization were also assessed and compared with those measured in nine non-diabetic children. The restoration of normoglycaemia was accompanied by hypoglucagonaemia, hypoketonaemia, increased insulin:glucagon ratio and abnormal postmeal fall in free fatty acid levels in spite of normal fasting and post-prandial plasma free insulin levels. These changes suggesting increased insulin action were most pronounced in newly-diagnosed diabetic children. Possibly as a result of increased insulin action high carbohydrate, low fat utilization and increased food-induced thermogenesis were observed in the newly-diagnosed diabetic children. In the chronically-treated group these parameters were approaching the normal. Resting energy expenditure was normal in both groups of diabetics. These findings suggest that precise glycaemic control can be achieved only at the expense of some degree of peripheral hyperinsulinisation which leads to altered nutrient utilization and food-induced thermogenesis in the newly-diagnosed diabetic children.
Diabetes Res 1988 Mar
PMID:Resting energy expenditure and food-induced thermogenesis in diabetic children receiving continuous subcutaneous insulin infusion. 304 18

To gain insight into cellular events associated with the progression of obesity to diabetes, we have studied glucose metabolism and insulin responses in adipocytes from monkeys with spontaneous obesity. Over a 3- period, we studied animals which (A) remained relatively lean; (B) became obese (over 30 percent body fat) with normal glucose tolerance; (C) were obese and developed hyperinsulinemia (over 100 microU/ml); and (D) were obese and subsequently developed noninsulin-dependent diabetes (NIDDM) (fasting plasma glucose above 140 mg/dl and abnormal glucose tolerance test). Adipocyte glucose utilization, evaluated by conversion of 14-C-glucose to CO2 and lipids, was measured in the absence and presence of varying concentrations of insulin, using cells prepared from biopsy samples of subcutaneous abdominal fat. The major change in adipocyte metabolism was a decrease in basal and insulin-stimulated glucose utilization in NIDDM, relative to the enhanced responses observed in cells from the obese-hyperinsulinemic monkeys. Longitudinal studies of individual monkeys over 2-3 years led to the following additional observations regarding adipocyte glucose metabolism. Basal and insulin-stimulated glucose utilization dropped markedly as hyperinsulinemia progressed into diabetes. As impairments in glucose tolerance worsened in diabetes, adipocytes showed only a modest or negligible additional impairment in basal and insulin-stimulated glucose oxidation. Insulin binding was reduced in adipocytes from monkeys with obesity as compared to lean controls, and was similar in cells from monkeys with obesity and NIDDM. In the monkeys, obesity was initially associated with enhanced adipocyte metabolism. With the spontaneous development of NIDDM, glucose metabolism in adipocytes was depressed. The progression of metabolic events from hyperinsulinemia to NIDDM in monkeys includes cellular changes in insulin responses at the level of the adipocyte.
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PMID:Changes in insulin responses and binding in adipocytes from monkeys with obesity progressing to diabetes. 306 66

Pancreatic islets held in tissue culture before transplantation into artificially induced diabetics are not rejected. In animals and human identical twin transplants, the autoimmunity of naturally occurring diabetes may destroy islets, even if rejection is avoided. Therefore we studied whether autoimmune damage of islets can be avoided by pretransplant culture. Recipients were BB rats, which spontaneously developed diabetes. Donors were either Wistar Furth (WF) (major histocompatibility [MHC] identical to BB rats) or Lewis (MHC nonidentical to BB rats). Islets were inoculated into the portal vein either immediately after isolation or after 14 days in tissue culture (95% air, 5% CO2, 24 degrees C). Recipients of cultured islets received a single injection of 1 ml of antilymphocyte serum at the time of transplant. Recurrence of diabetes after transplantation of freshly isolated MHC incompatible Lewis islets occurred rapidly on the basis of rejection or autoimmune damage (or both). Precultured Lewis islets had prolonged or permanent survival. Freshly isolated MHC compatible WF islets were destroyed, and no improvement was seen with culture. We conclude that autoimmune destruction of transplanted islets can be avoided by tissue culture, as can rejection. This is important because this strategy is effective only if recipient and donor differ at the MHC locus. Islet donors may need to be selected on the basis of disparity of histocompatibility factors.
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PMID:Transplantation of cultured pancreatic islets to BB rats. 309 Jul 24

The combination of donor pretreatment with cyclophosphamide, organ culture in 95% O2:5% CO2 for 7-10 days, and short-term immunosuppression of recipients with cyclosporin A (CsA) were necessary to obtain 100% survival of single-cluster BALB/c islet allografts in outbred mice. In vivo and in vitro pretreatment of the donor tissue alone resulted in the acceptance of 45% of the islet allografts in nonimmunosuppressed outbred mice. CsA treatment of recipients alone yielded 40% survival of the untreated allografts. CsA treatment played an important role in maintaining the capacity of islet allografts to function in outbred mice. During CsA treatment, 88% of streptozocin-treated mice showed graft-dependent reversal of diabetes; the remainder showed no evidence of graft function, and CsA treatment failed to prevent acute graft rejection. After withdrawal of CsA immunosuppression, 38% of this total group remained normoglycemic. These findings suggest that modulation of both donor-tissue immunogenicity and recipient responsiveness will be required for successful pancreatic islet transplantation in diabetic humans.
Diabetes 1986 Dec
PMID:Reversal of diabetes in outbred mice by islet allotransplantation. 309 65

Alloxan-induced diabetes in rats significantly impaired the capacity of the erythrocytes to metabolise glucose in vitro to either lactic acid or CO2. Both these metabolic activities were initially insensitive to insulin in normal as well as in diabetic animals; but became responsive when these cells were subjected to insulin and glucose 'starvation' for 1 h through incubation in their absence. This action of insulin in starved cells showed concentration dependence and required preincubation with the hormone prior to addition of glucose.
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PMID:In vitro insulin action on erythrocyte glucose metabolism in normal and diabetic rats. 312 60


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