Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Estimates of the quantitative contribution of adipose tissue to whole-body glucose metabolism, previously reported as 1-3%, have been revised to be on the order of 10-30%. These revised estimates come, in part, from a recognition that adipose tissue uses glucose to produce lactate and pyruvate, in addition to CO2 and triglycerides. Lactate production by adipose tissue is modulated in vitro by changes in glucose, insulin, and epinephrine concentrations. In vivo, lactate production is regulated acutely by the animal's nutritional state (fed or fasted) and chronically by the degree of obesity. A strong positive correlation exists between rat fat cell size and relative conversion of glucose to lactate (r = 0.89, P less than 0.001). Diabetes is also associated with markedly increased lactate production in adipocytes. Fat cells from obese or diabetic rats (or humans) can metabolize to lactate as much as 50-70% of the glucose taken up. From these recent studies, a picture is emerging in which the adipose organ may provide lactate for hepatic gluconeogenesis during fasting, and also lactate for hepatic glycogen synthesis after food ingestion. Modulation of adipocyte lactate production and contribution of adipose tissue lactate to the body's fuel economy in physiological and pathological states are the focus of this review.
...
PMID:Lactate production in adipose tissue: a regulated function with extra-adipose implications. 156 93

The French incidence study has registered all new cases of Type 1 diabetic children under 20 years of age, from a population of 2.32 million, in an exhaustive and prospective manner. Three hundred and forty cases were identified between 1 January 1988 and 31 December 1989, yielding a mean annual incidence rate 7.3 per 10(5). The lowest rate was observed in the youngest age group (0-4 yr: 4.1 per 10(5)) and the highest around pubertal development (10-14 yr: 11.5 per 10(5)). Details of the previous personal and family history, and the clinical and biological pictures of the disease at diagnosis were recorded. Almost 8 per cent of the children had a first-degree relative with Type 1 diabetes. Polyuria, weight loss, fatigue and abdominal pain were the most frequently reported symptoms, which were of median duration 4.4 months. Mean weight loss before diagnosis was 9.4 +/- 6.8 (+/- SD)% of body weight and was not significantly related to age. Ketonuria was detected in 83.8 per cent and acidosis (total CO2 less than or equal to 18 mmol l-1, if measured) in 48 per cent of the cases. Ketonuria and acidosis were significantly more frequent in the younger age group than in the rest of the group (p less than 0.001).
...
PMID:Clinical and laboratory features of type 1 diabetic children at the time of diagnosis. 157 13

To investigate the metabolic fates of glutamine in splenocytes from the BB rat with spontaneous immunologically mediated insulin-dependent diabetes, freshly isolated cells were incubated in Krebs-Ringer Hepes buffer with 1.0 mM-[U-14C]glutamine and 0, 4 mM- or 15 mM-glucose. (1) The major products of glutamine metabolism in splenocytes from normal and diabetic rats were ammonia, glutamate, aspartate and CO2. (2) The addition of glucose increased (P less than 0.01) glutamate production, but decreased (P less than 0.01) aspartate and CO2 production from glutamine, as compared with the values obtained in the absence of glucose. However, there were no differences in these metabolites of glutamine at 4 mM- and 15 mM-glucose. (3) At all glucose concentrations used, the productions of ammonia, glutamate, aspartate and CO2 from glutamine were all markedly increased (P less than 0.01) in splenocytes from diabetic rats. (4) Potential ATP production from glutamine in the splenocytes was similar to that from glucose, and was increased in cells from the diabetic rat. (5) ATP concentrations were increased (P less than 0.01) in diabetic-rat splenocytes in the presence of glutamine with or without glucose. (6) Our results demonstrate that glutamine is an important energy substrate for splenocytes and suggest that the increased glutamine metabolism may be associated with the activation of certain subsets of splenocytes in the immunologically mediated diabetic syndrome.
...
PMID:Elevated glutamine metabolism in splenocytes from spontaneously diabetic BB rats. 167 65

Denervated muscle is generally regarded as insulin resistant because the ability of insulin to stimulate glucose transport and glycogen synthesis is impaired. Previous studies indicate that insulin resistance in these muscles is likely due to a defect at a postreceptor site in the signaling pathway. Because glucose transport into cells has been reported to be linked to changes in diacylglycerol (DAG) and protein kinase C (PKC), we investigated the effect of denervation on the content and synthesis of DAG and the activity and distribution of PKC in the soleus muscle. The DAG content in muscles denervated for 24 h was 40% greater than in control muscles. This was associated with a two- to threefold increase in the percentage of total PKC activity that was membrane associated, with no significant change in total PKC activity, suggesting an increase in PKC activity in vivo. Studies of glucose disposition confirmed that the stimulation of glycogen synthesis by insulin and, to a lesser extent, 2-deoxyglucose uptake were impaired by denervation. However, the stimulation by insulin of glucose incorporation into DAG and other lipids was two- to threefold greater in denervated than in control muscles, and conversion of glucose to lactate and pyruvate and glucose oxidation to CO2 were unchanged. The results reveal a dichotomy in the effects of denervation on various actions of insulin, with both insulin resistance and hyperresponsiveness occurring in different pathways of glucose metabolism. They also reveal a potential mechanism for the elevation of muscle DAG after denervation. The results do not support a direct link between DAG-PKC and glucose transport.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1991 Dec
PMID:Enhanced stimulation of diacylglycerol and lipid synthesis by insulin in denervated muscle. Altered protein kinase C activity and possible link to insulin resistance. 175 11

Metabolism of glutamine (Gln, 2 mM) and glucose (5 mM) was studied in vitro in isolated resident peritoneal macrophages from both normal (BBn) and spontaneously diabetic BB (BBd) rats. The major products from Gln were ammonia, glutamate, CO2 and to a lesser extent aspartate. Glucose decreased (P less than 0.01) the production of ammonia, CO2 and aspartate from Gln by 34-60%, but had no effect on the amount of glutamate accumulated. The major products from glucose were lactate and to a much lesser extent pyruvate and CO2. Gln decreased (P less than 0.01) 14CO2 production from [U-14C]glucose by 19-28%, increased (P less than 0.01) pyruvate production by 35-49%, but had no effect on lactate production. The fraction of glucose metabolized via the pentose phosphate pathway (PC) was less than 5%. There were no significant differences in Gln metabolism between BBn and BBd macrophages. The production of lactate and pyruvate and the flux from glucose into the PC were increased (P less than 0.01) by 2.4, 1.8 and 1.5-fold, respectively, in BBd cells. Increased macrophage glucose metabolism was also observed in diabetes-prone BB (BBdp) rats at 75-80 days but not at 50 days of age. In the presence of both Gln and glucose, potential ATP production from glucose was 2- and 4-times that from Gln, respectively, in BBn and BBd cells. Lactate production was the major pathway for glucose-derived ATP generation. These results demonstrate (a) glycolysis and flux from glucose through the pentose phosphate pathway are enhanced with no alteration in glutaminolysis in BBd macrophages; and (b) glucose may be a more important fuel than Gln for macrophages, particularly in BBd rats. The increased glucose metabolism may be associated with functional activation of the macrophages that have been proposed to be involved in beta-cell destruction and the development of diabetes.
...
PMID:Glucose and glutamine metabolism in rat macrophages: enhanced glycolysis and unaltered glutaminolysis in spontaneously diabetic BB rats. 176 69

Fifteen spontaneously diabetic, non-obese mice (NOD strain), 17 non-diabetic NOD mice (in which diabetes had not yet developed) and 9 diabetic NOD mice were treated with insulin. All animals were superovulated with 5 iu of pregnant mares' serum gonadotrophin followed 48 h later by 5 iu human chorionic gonadotrophin (hCG) and mated overnight with NOD males of proven fertility. To assess in-vitro and early in-vivo development, 23 NOD mice were killed 72 h after hCG treatment. Embryos were recovered from oviduct flushings and cultured in Ham's F-10 medium with 0.1% bovine serum albumin at 37 degrees C in an atmosphere of 5% O2, 5% CO2, and 90% N2. Development was assessed at intervals of 24 h for 72 h. Compared with embryos from non-diabetic NOD mice (n = 81), embryos from diabetic NOD mice (n = 68) demonstrated marked impairment in growth assessed by distribution of developmental stages at each observation period (24, 48, 72 h, all P less than 0.001) and by overall rates of progression of developmental stages (P less than 0.01). In diabetic NOD mice treated with insulin, embryo development (n = 7) was not significantly different from that of embryos from non-diabetic NOD mice (n = 81), but was significantly faster than in embryos from diabetic NOD mice not treated with insulin (n = 68) (P less than 0.001, for all periods, overall rate P less than 0.01). To assess late in-vivo growth, 18 NOD mice were killed 120 h after hCG.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of diabetes mellitus on mouse pre-implantation embryo development. 178 51

In islets from adult rats injected with streptozocin during the neonatal period, the oxidative and secretory responses to D-glucose are more severely affected than those evoked by L-leucine. A possible explanation for such a preferential defect was sought by comparing the rate of aerobic glycolysis, taken as the sum of D-[3,4-14C]glucose conversion to labeled CO2, pyruvate, and amino acid, with the total glycolytic flux, as judged from the conversion of D-[5-3H]glucose to 3H2O. A preferential impairment of aerobic relative to total glycolysis was found in islets from diabetic rats incubated at either low or high D-glucose concentration. This coincided in islet mitochondria of diabetic rats with a severe decrease in both the basal (no-Ca2+) generation of 3H2O from L-[2-3H]glycerol-3-phosphate and the Ca2(+)-induced increment in [3H]glycerophosphate detritiation. The mitochondria of diabetic rats were also less efficient than those of control animals in generating 14CO2 from [1-14C]-2-ketoglutarate. The diabetes-induced alteration of 2-ketoglutarate dehydrogenase in islet mitochondria was less marked, however, than that of the FAD-linked glycerophosphate dehydrogenase and was not associated with any change in responsiveness to Ca2+. Sonicated islet mitochondria of diabetic rats displayed normal to slightly elevated glutamate dehydrogenase activity. We propose, therefore, that the preferential impairment of the oxidative and secretory responses of islet cells to D-glucose in this experimental model of diabetes may be at least partly attributable to an altered transfer of reducing equivalents into the mitochondria as mediated by the glycerol phosphate shuttle.
Diabetes 1991 Feb
PMID:Impairment of glycerol phosphate shuttle in islets from rats with diabetes induced by neonatal streptozocin. 182 72

We used the fluorescent dye 2',7'-bis-(2-carboxyethyl)-5(6)-carboxyfluorescein (BCECF) to examine intracellular pH (pHi) regulation in single hepatocytes isolated from control rats and rats with either spontaneous or drug-induced diabetes mellitus (DM). In the absence of CO2-HCO3-, both control and DM cells recovered from cellular acid loads applied by the NH4+ prepulse technique. Because the pHi recovery was blocked by either Na+ withdrawal or ethylisopropylamiloride in both control and DM cells, it was presumably mediated by Na(+)-H+ exchange. In the control cells, the pHi threshold above which the rate of change of pHi (dpHi/dt) was zero was 7.06, and the slope of the dpHi/dt-pHi relationship was -0.030 s-1. In the DM cells, the pHi threshold was 7.22 and the slope was -0.017 s-1. Thus, at pHi values below approximately 6.9, the pHi recovery was slower in the DM cells. Inasmuch as we observed no difference in the cellular buffering power between control and DM cells, diabetes inhibits Na(+)-H+ exchange within this low pHi range. At pHi values above approximately 6.9, however, Na(+)-H+ exchange was apparently stimulated by diabetes. Thus diabetes induces two distinct alterations of Na(+)-H+ exchange, an alkaline shift in pHi threshold and decrease in slope. Treatment of diabetic rats with insulin for 48 h restored both Na(+)-H+ exchange parameters to normal. On the other hand, insulin added in vitro to DM cells for 2-5 h shifted the threshold toward the control value without affecting the slope, thus leading to a further inhibition of Na(+)-H+ exchange over the entire pHi range.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Effect of diabetes on Na(+)-H+ exchange by single isolated hepatocytes. 184 69

We have previously reported a decrease in gluconeogenesis from alanine in normal pregnant women at term gestation as compared with nonpregnant women. In the present study, the effect of diabetes on alanine metabolism was examined in five gestationally diabetic (GDM) women and seven women with type I (insulin-dependent) diabetes (IDDM) during the third trimester of pregnancy. The hemoglobin A1c (HbA1c) concentrations in all subjects were within normal range, indicating good metabolic control. After an overnight fast, each subject was infused simultaneously with L-[2,3, 13C2]alanine and D-[6,6,2H2]glucose tracers as prime constant rate infusion. Plasma alanine and glucose isotopic enrichments were measured by gas chromatography-mass spectrometry. Alanine and glucose turnover rates were quantified by tracer dilution. In five subjects, the contribution of alanine carbon to CO2 was quantified by respiratory calorimetry and by measurement of 13C enrichment of expired CO2. Data from 15 previously reported normal pregnant subjects were used for comparison. The rate of alanine turnover was similar in the GDM and IDDM subjects and was not different from the normal subjects (GDM, 4.6 +/- 1.9; IDDM, 5.4 +/- 2.5; normals, 4.4 +/- 0.8 mumol/kg.min, mean +/- SD). The rate of glucose turnover was significantly reduced (P less than .05) in IDDM as compared with GDM and normal subjects (IDDM, 8.1 +/- 0.8; GDM, 11.5 +/- 3.5; normals, 12.2 +/- 2.2 mumol/kg.min). The contribution of alanine C to glucose C and expired CO2 was similar in the three groups. These data demonstrate that rigorous metabolic control results in normal glucose and alanine metabolism in diabetic pregnancy during fasting.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Glucose-alanine relationship in diabetes in human pregnancy. 190 12

The natural history of tissue repair and the critical determinants of faulty healing of diabetic ulcers remain obscure despite recent advances in our knowledge of the cellular physiology of normal cutaneous healing. To characterize the chronology and identify important factors affecting healing, we applied an objective method to quantify the rate of wound healing of full-thickness lower-extremity ulcers in 46 diabetic outpatients who received local wound care under a standardized clinical protocol. The initial ulcer healing rate, eventual status of tissue repair, and definitive clinical outcome were not significantly associated with age; diabetes type, duration, or treatment; level or change in glycosylated hemoglobin; current smoking; presence of sensory neuropathy; ulcer location or class; initial infection; or frequency of recurrent infections. However, direct measures of local cutaneous perfusion, estimated by periwound measurements of transcutaneous O2 tension (TcPo2) and transcutaneous CO2 tension (TcPco2), were significantly associated with the initial rate of tissue repair (P = 0.003 and 0.005, respectively). The strong prediction of early healing by these parameters of local skin perfusion was independent from the effects of segmental Doppler arterial blood pressure at the dorsalis pedis, although eventual ulcer reepithelialization was significantly related to foot blood pressure and periwound TcPo2 and TcPco2. We conclude that periwound cutaneous perfusion is the critical physiological determinant of diabetic ulcer healing, indicating a 39-fold increased risk of early healing failure when the average periwound TcPo2 is less than 20 mmHg.
Diabetes 1991 Oct
PMID:Chronology and determinants of tissue repair in diabetic lower-extremity ulcers. 193 93


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---