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

Attenuation, suppression or even inversion of the normal preference of glucose-stimulated insulin release for the alpha-anomer of the hexose was recently proposed to represent a feature of Beta-cell glucotoxicity in Type 2 (non-insulin-dependent) diabetes mellitus. Since recent reports emphasize the possible significance of Beta-cell secretory hyperactivity as a determinant of such a glucotoxicity, the anomeric specificity of glucose-induced insulin release was examined in normoglycaemic partially pancreatectomized rats. About 80-85% of the pancreas was removed, the animals then being given sucrose via their drinking water up to the time of killing. In these animals, alpha-D-glucose was more efficient than beta-D-glucose in stimulating insulin release from the perfused pancreas, the alpha/beta ratio in insulin output not being significantly different from that found in control rats. It is concluded, therefore, that the anomeric malaise, taken as a manifestation of Beta-cell glucotoxicity, it attributable to hyperglycaemia rather than to Beta-cell secretory hyperactivity.
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PMID:Preservation of the anomeric specificity of glucose-induced insulin release in partially pancreatectomized rats. 161 22

Amylin, a peptide found in pancreatic amyloid deposits, may be involved in NIDDM. The effects of biosynthetic human amylin on multiple aspects of carbohydrate metabolism were studied in freshly isolated and cultured liver cells (rat hepatocytes and HepG2 cells). Acute exposure of culture liver cells to amylin had no effect on glucose incorporation into glycogen. Amylin directly reduced glucose oxidation through the hexose monophosphate shunt. The glycolytic pathway was unaffected. Amylin stimulated both glycogenolysis and gluconeogenesis. These effects were largest at amylin concentrations of 1-10 pM. Insulin partially inhibited both of these responses. Glucagon stimulated glycogenolysis and gluconeogenesis to a similar extent as amylin but required concentrations 100- to 500-fold as high. Thus, amylin, at physiologic concentrations, can impair some aspects of glucose use in liver cells and is also capable of directly stimulating glucose production, suggesting a possible involvement of amylin in the impaired glucose disposal and elevated hepatic glucose output of NIDDM.
Diabetes 1992 Aug
PMID:In vitro effects of amylin on carbohydrate metabolism in liver cells. 162 73

The effects of Zn2+ in mimicking insulin in vivo and in vitro are further characterized. Like insulin, Zn2+ stimulated the conversion of [U-14C]-, [1-14C]-, and [6-14C]glucose to lipids in rat adipocytes. Maximum stimulation of lipogenesis was 55-80% of maximum insulin response after preincubation (30 min at 37 degrees C) of adipocytes with ZnCl2 (0.4 mM). Under these conditions, the half-maximum effect was achieved at 0.17 +/- 0.02 mM of ZnCl2. Similarly, an insulinlike effect of Zn2+ was observed on the oxidation of glucose by both pathways, glycolytic and hexose monophosphate shunt. In contrast, unlike insulin, Zn2+ did not inhibit lipolysis but rather exhibited a slight lipolytic activity. Also, the effect of Zn2+ on hexose influx did not exceed 14 +/- 3% that of insulin. The stimulatory effects of Zn2+ were not related to generation of H2O2. Catalase (100 micrograms/ml) did not inhibit Zn(2+)-stimulated glucose oxidation and its incorporation into lipids. Zn2+ had an additive effect on either insulin- or vanadate-stimulated conversion of [1-14C]glucose to fat, and together, the effect was approximately 140% of the maximum rate of lipogenesis. Chelation of intracellular Zn2+ by the cell-permeable chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine did not significantly affect the ability of insulin to stimulate lipogenesis. Adipocytes derived from STZ rats were largely refractory to the modulating action of insulin. In contrast, the effect of Zn2+ on lipogenesis in these cells was more pronounced.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Aug
PMID:Insulinlike effects of zinc ion in vitro and in vivo. Preferential effects on desensitized adipocytes and induction of normoglycemia in streptozocin-induced rats. 162 74

The objectives of this study were 1) to evaluate glucose transport and its regulation by insulin in easily accessible human cells, 2) to investigate the glucose transporter isoforms involved, and 3) to establish whether a defect in glucose transport is associated with peripheral insulin resistance, which is common in insulin-dependent diabetes mellitus (IDDM) patients. We measured 2-deoxyglucose (2-DG) uptake in circulating mononuclear cells from 23 nondiabetic adults, 16 adults with IDDM, and 10 children with IDDM. Circulating mononuclear cells were separated from whole blood by Ficoll gradients and incubated with +/- 1 nM insulin. 2-DG uptake was measured after incubation with [3H]2-DG and cell separation through corn oil-phthalate. Cytochalasin B-inhibitable 2-DG uptake (basal and insulin stimulated) was higher in control than in IDDM subjects (P less than 0.001). Insulin significantly increased 2-DG uptake or 3-O-methylglucose uptake in both groups. Basal and insulin-stimulated 2-DG uptake was similar for adults and children with IDDM and did not correlate with age or body mass index in any group or disease duration, insulin dosage, or HbA1c in IDDM. In separated monocytes and lymphocytes, 2-DG uptake increased in response to insulin only in the monocyte population. Insulin dose-response curves indicated maximal stimulation of hexose uptake at 1-2 nM insulin for both control and diabetic subjects and demonstrated a significant decrease in maximal insulin response in the latter. Immunoblotting with specific antibodies revealed that circulating mononuclear cells and separated monocytes express the GLUT1 but not the GLUT4 isoform of the glucose transporter.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1992 Feb
PMID:Insulin-stimulated glucose transport in circulating mononuclear cells from nondiabetic and IDDM subjects. 173 14

Recent information suggests that type 2 diabetes mellitus (NIDDM) is associated with severe insulin resistance, but other information suggests that there is a hypoinsulinemic state. To investigate the nature of the insulin resistance, 10 newly diagnosed, mildly obese type 2 diabetics and 11 long-standing type 2 diabetics with secondary failure to sulfonylureas were studied. Insulin was given by continuous subcutaneous infusion (CSII) for two weeks. CSII produced near-normoglycemia after 1-4 days in all patients with modest amounts of insulin (0.5-0.9 U/kg/24 h). These results demonstrate that whatever insulin resistance prevails in NIDDM, it does not prevent induction of normoglycemia by insulin. This suggests that either the insulin resistance is a secondary event caused by hyperglycaemia, or that NIDDM patients are hypoinsulinemic. In further studies in vitro, the effect of glucose on the rate of glycolytic glucose utilization by isolated rat soleus muscle and on hexose transport in rat skeletal myocyte line L8 were assessed. In the first case, an increase in glucose concentration led to a decrease in muscle glycolysis, and in the second case a hyperglycemic concentration of glucose led to a marked reduction in hexose transport, which was fully reversible within two hours. The clinical and in vitro results plus literature data suggest that insulin resistance can be overcome by insulin in NIDDM, and that beta-cell responsiveness to glucose is greatly reduced in NIDDM, but the defect is restricted to the acute stimulatory phase of glucose induction of insulin release. If this defect can be corrected, acute insulin release will occur so that NIDDM would be cured notwithstanding the existence of insulin resistance.
Diabetes Res Clin Pract 1991
PMID:Insulin resistance, insulin deficiency, and non-insulin-dependent diabetes mellitus. 179 64

We studied the transport rate of a non-metabolizable hexose analogue, 3-O-methyl-D-glucose, in polymorphonuclear leukocytes (insulin-insensitive cells) from patients with untreated non-insulin-dependent diabetes mellitus. The mean glucose transport rate was significantly elevated in the diabetic patients compared with healthy controls (13.3 +/- 3.7 vs 10.4 +/- 2.5 fl/cell.sec, mean +/- SD, p less than 0.01). In the diabetic subjects, glucose transport rates were positively correlated with HbA1c levels (r = 0.563, p less than 0.01) but had no relations with ambient plasma glucose concentrations. Short-term incubation with 20 mM D-glucose had no effect on glucose transport in those cells. When glucose transport rates, HbA1c and fasting plasma glucose levels were simultaneously measured at weekly intervals over a four-week period in three diabetic subjects, the alterations in transport rates generally paralleled the changes observed in HbA1c levels rather than plasma glucose concentrations. It can be concluded that unlike insulin-sensitive cells such as adipocytes and muscle, glucose transport in human polymorphonuclear leukocytes, which are insulin insensitive cells, is increased in patients with non-insulin-dependent diabetes mellitus. Long-term, not short-term, derangement of glucose metabolism seems to be associated with increased glucose transport rate found in those patients.
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PMID:Increased insulin-insensitive glucose transport in polymorphonuclear leukocytes from non-insulin-dependent diabetic patients. 179 43

Isotopic discrimination in reaction velocity may affect to a variable extent the estimation of metabolic flow when a metabolic intermediate is catabolized by two pathways with different degrees of discrimination. This was explored in erythrocytes exposed to 14C- or 3H-labelled D-glucose in the absence or presence of menadione. In the absence of menadione, when the pentose phosphate pathway accounted for only 5% of the D-glucose 6-phosphate turnover, the oxidation of C1-protonated or C1-deuterated D-[U-14C]glucose and D-[1-14C]glucose, mixed with the homologous non-radioactive D-[1-1H]glucose or D-[1-2H]glucose, indicated that, relative to the phosphorylation of the hexose, C1-deuterated D-glucose was less efficiently converted to 14CO2 than C1-protonated D-glucose. Moreover, in the absence of menadione, non-deuterated D-[U-14C]glucose and D-[1-14C]glucose were more efficiently oxidized in cells exposed to D-[1-2H]glucose rather than D-[1-1H]glucose. In the presence of menadione, which increased more than ten-fold the flow rate through the pentose phosphate pathway, the phenomenon of isotopic discrimination was either revealed or masked. These data indicate that the phenomenon of isotopic discrimination may indeed affect to a variable extent the estimation of a given metabolic flow.
Diabetes Res 1991 Jun
PMID:Variable expression of isotopic discrimination in metabolic flows. 181 12

The relationship between glucose oxidation and glycolysis was examined in tumoral pancreatic islet cells with either rapid or decreased cell growth. In the control RINm5F cells, the utilization of D-[5-3H]glucose progressively augmented at increasing concentrations of D-glucose (0.2 to 16.7 mM), whereas D-[6-14C]glucose oxidation reached its maximal value at about 3.0 mM D-glucose. The 14CO2/3HOH ratio progressively decreased at increasing hexose concentrations, being about 5-times higher at 0.2 than 10.0-16.7 mM. These experiments were repeated in cells cultured in the presence of D,L-alpha-difluoromethylornithine, which inhibits RINm5F cell proliferation. At 0.2 mM D-glucose, 14CO2 output was severely decreased but 3HOH production little affected, resulting in a marked fall of the 14CO2/3HOH ratio. On the contrary, at 16.7 mM D-glucose, 3HOH formation was more markedly decreased than 14CO2 output, resulting in an increased 14CO2/3HOH ratio. These findings provide a model for the interference of cell growth with D-glucose metabolism in islet cells. Rapid growth causes a preferential stimulation of the Krebs cycle relative to glycolysis at a low glucose concentration, whilst increasing glycolysis more than oxidation at high concentrations of the hexose.
Diabetes Res 1991 Jun
PMID:Relationship between D-glucose oxidation and glycolysis in tumoral pancreatic islet cells with either rapid or decreased cell growth. 181 13

Several studies in the last decade have highlighted the importance of the hexose sugars and especially glucose, as being responsible for alterations to living protein and other molecules. The phenomenon of nonenzymatic glycation--by which the carbonyl group of glucose can directly condense with a free amino group--may be relevant for the process of aging and for the pathogenesis of late diabetic complications. Thus life-long exposure to normoglycemia in non diabetic subjects or a shorter exposure but continued association with a hyperglycemic milieu, as in diabetes mellitus, have both been shown to lead to the formation and accumulation of irreversible and highly reactive advanced glycation endproducts (AGE) over long-lived, fundamental molecules such as the constituents of arterial wall collagen, basement membranes, nerve myelin, DNA and others. For example, the introduction of foreign AGE groups into proteins might alter their tertiary structure and therefore modify their function or activity. By increasing protein-to-protein cross-links AGE could reduce protein turnover, with consequential increases in levels of modified and thus less reactive molecules. Moreover, AGE could initiate an immune response with the production of specific antibodies. Reducing the extent of nonenzymatic glycation could effectively reduce the accumulation of AGE. Many authors are experimenting with methods to achieve this aim. Amongst the products tested are aspirin and aminoguanidine which compete with glucose for the same protein amino group. D-lysine is also being investigated on the principle that by reacting with glucose in circulation, it could effectively prevent it from reaching the amino group on the protein.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes Res 1991 Jan
PMID:Advanced nonenzymatic glycation endproducts (AGE): their relevance to aging and the pathogenesis of late diabetic complications. 181 91

The fate of D-[2-3H] glucose and D-[5-3H] glucose in pancreatic islets was simulated in models with or without enzyme-to-enzyme tunnelling of hexose 6-phosphates in the glycolytic cascade. Satisfactory values for the recovery of phosphoglucoisomerase activity, for the ratio between unlabelled D-glucose 6-phosphate and D-fructose 6-phosphate, and for the time course of both 3HOH production from D-[2-3H] glucose and tritiated D-fructose 1,6-bisphosphate generation from D-[5-3H] glucose were only reached in models with enzyme-to-enzyme tunnelling, with emphasis on the coupling between phosphoglucoisomerase and phosphofructokinase.
Diabetes Res 1991 Jan
PMID:Hexose metabolism in pancreatic islets (time course of 3HOH production from tritiated D-glucose in models with and without enzyme-to-enzyme tunnelling). 181 93


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