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

The objective of the study was to examine the potential differential effect of insulin and acipimox (both of which reduce free fatty acid [FFA] availability) on VLDL apolipoprotein (apo) B metabolism. We studied eight healthy men (age 40 +/- 4 years, BMI 25.8 +/- 0.9 kg/m2, plasma triglycerides 1.30 +/- 0.12 mmol/l) after an overnight fast (control study, n = 8), during inhibition of lipolysis with an antilipolytic agent, acipimox (n = 8), and under 8.5-h euglycemic-hyperinsulinemic conditions (n = 5). Plasma FFAs were similarly suppressed in the acipimox and insulin studies (approximately 70% suppression). 2H3-leucine was used to trace apo B kinetics in VLDL1 and VLDL2 subclasses (Svedberg flotation rates: 60-400 and 20-60), and a non-steady-state multicompartmental model was used to derive the kinetic constants. The mean rate of VLDL1 apo B production was 708 +/- 106 mg/day at the beginning and 602 +/- 140 mg/day at the end of the control study. Production of the lipoprotein decreased to 248 +/- 93 mg/day during the insulin study (P < 0.05 vs. control study) and to 375 +/- 92 mg/day (NS) during the acipimox study. Mean VLDL2 apo B production was significantly increased during the acipimox study (399 +/- 42 vs. 236 +/- 27 mg/day, acipimox vs. control, P < 0.05) but not during the insulin study (332 +/- 51 mg/day, NS). The fractional catabolic rates of VLDL1 and VLDL2 apo B were similar in all three studies. We conclude that acute lowering of FFAs does not change the overall production rate of VLDL particles, but there is a shift toward production of smaller and denser VLDL2 particles, and, thus, the amount of total VLDL particles secreted remained constant. Insulin acutely suppresses the total production rate of VLDL apo B by decreasing the production of large triglyceride-rich VLDL1 particles. Based on these findings, we postulate that insulin has a direct suppressive effect on the production of VLDL apo B in the liver, independent of the availability of FFAs.
Diabetes 1998 May
PMID:Effects of insulin and acipimox on VLDL1 and VLDL2 apolipoprotein B production in normal subjects. 958 50

To measure myocardial blood flow, Nitrogen-13 ammonia. Oxygen-15 water, Rubidium-82 and et al. are used. Each has merit and demerit. By measuring myocardial coronary flow reserve, the decrease of flow reserve during dipyridamole in patients with hypercholesterolemia or diabetes mellitus without significant coronary stenosis was observed. The possibility of early detection of atherosclerosis was showed. As to myocardial metabolism, glucose metabolism is measured by Fluorine-18 fluorodexyglucose (FDG), and it is considered as useful for the evaluation of myocardial viability. We are using FDG to evaluate insulin resistance during insulin clamp in patients with diabetes mellitus by measuring glucose utilization rate of myocardium and skeletal muscle. FFA metabolism has been measured by 11C-palmitate, but absolute quantification has not been performed. Recently the method for absolute quantification was reported, and new radiopharmaceutical 18F-FTHA was reported. Oxygen metabolism has been estimated by 11C-acetate. Myocardial viability, cardiac efficiency was evaluated by oxygen metabolism. As to receptor or sympathetic nerve end, cardiac insufficiency or cardiac transplantation was evaluated. Imaging of positron emitting radiopharmaceutical by gamma camera has been performed. Collimator method is clinically useful for cardiac imaging of viability study.
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PMID:[The review of myocardial positron emission computed tomography and positron imaging by gamma camera]. 964 28

A line of transgenic rats (heterozygotes) carrying a chimeric gene comprising a regulatory portion of murine whey acidic protein and a structural portion of human GH (hGH) genes developed severe obesity with age. To characterize physiological mechanisms that lead to fat accumulation, an array of parameters related to obesity were studied. Blood hGH levels were continuously low, endogenous rat GH secretion was suppressed, and the pulsatility in peripheral GH levels was absent. Plasma glucose, insulin, triglyceride, and FFA levels in the male transgenic rats significantly exceeded those in nontransgenic littermates at 12 and 17 weeks, but not at 7 weeks, of age. All symptoms except hyperlipidemia were restored to normal by treatment with an antidiabetic agent, thiazolidinedione (troglitazone), for 1 week from 17 weeks of age. As phenotypic expression of obesity was already evident before aberration of physiological parameters, it was assumed that animals had a condition in which obesity or hyperlipidemia caused hyperinsulinemia. Gene expression and enzymatic activity of lipoprotein lipase in the adipose tissue in the transgenic rats were not different from those in normal rats. In contrast, the gene expression level of glycerol-3-phosphodehydrogenase was markedly elevated, suggesting that glycerol synthesis was much enhanced in the adipocytes of the transgenic rats. In an i.p. glucose tolerance test, the transgenic rats were not hyperglycemic at 7 weeks of age; however, the animal became hyperglycemic at 15-17 weeks of age. Finally, treatment with recombinant hGH for 1 week to produce pulsatile secretion reduced the size of epididymal and kidney fat pads and restored normal weight gain. These observations suggest that continuously low peripheral GH levels with the lack of pulsatile secretion resulted in obesity and noninsulin-dependent diabetes mellitus.
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PMID:Obesity and insulin resistance in human growth hormone transgenic rats. 964 76

Release of glucose by liver and kidney are both increased in diabetic animals. Although the overall release of glucose into the circulation is increased in humans with diabetes, excessive release of glucose by either their liver or kidney has not as yet been demonstrated. The present experiments were therefore undertaken to assess the relative contributions of hepatic and renal glucose release to the excessive glucose release found in type 2 diabetes. Using a combination of isotopic and balance techniques to determine total systemic glucose release and renal glucose release in postabsorptive type 2 diabetic subjects and age-weight-matched nondiabetic volunteers, their hepatic glucose release was then calculated as the difference between total systemic glucose release and renal glucose release. Renal glucose release was increased nearly 300% in diabetic subjects (321+/-36 vs. 125+/-15 micromol/min, P < 0.001). Hepatic glucose release was increased approximately 30% (P = 0.03), but increments in hepatic and renal glucose release were comparable (2.60+/-0.70 vs. 2.21+/-0.32, micromol.kg-1.min-1, respectively, P = 0.26). Renal glucose uptake was markedly increased in diabetic subjects (353+/-48 vs. 103+/-10 micromol/min, P < 0.001), resulting in net renal glucose uptake in the diabetic subjects (92+/-50 micromol/ min) versus a net output in the nondiabetic subjects (21+/-14 micromol/min, P = 0.043). Renal glucose uptake was inversely correlated with renal FFA uptake (r = -0.51, P < 0.01), which was reduced by approximately 60% in diabetic subjects (10. 9+/-2.7 vs. 27.0+/-3.3 micromol/min, P < 0.002). We conclude that in type 2 diabetes, both liver and kidney contribute to glucose overproduction and that renal glucose uptake is markedly increased. The latter may suppress renal FFA uptake via a glucose-fatty acid cycle and explain the accumulation of glycogen commonly found in the diabetic kidney.
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PMID:Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus. 969 Oct 98

A 71-year-old woman was admitted to our hospital because of severe hypertriglyceridemia. The patient had a 26-year history of non-insulin-dependent diabetes mellitus and hyperlipidemia (T-chol 300 mg/dl, TG 300 mg/dl). She was treated with sulfonylurea and clofibrate. Seven years before admission, she had undergone a radical mastectomy for cancer of the left breast. After the operation, she had received tamoxifen and fluorouracil. One month before admission, she had marked hypertriglyceridemia (triglyceride 2,106 mg/dl). After discontinuation of tamoxifen and fluorouracil, her serum triglyceride level decreased to 372 mg/dl; when tamoxifen was given again, it increased to 581 mg/dl, and her hepatic triglyceride lipase activity decreased from 0.228 to 0.164 mumol FFA/ml/min. Apolipoprotein E phenotype was wild type E3/3. The concentration of sex-hormone-binding globulin increased from 110 to 130 nmol/l. These changes associated with tamoxifen treatment were similar to those seen after administration of estrogen. Tamoxifen, an anti-estrogen, has been used as adjuvant therapy in cases of estrogen-receptor-positive breast cancer. Tamoxifen has some weak estrogenic activity. The tamoxifen-induced hypertriglyceridemia seen in this case was an effect of its estrogenic action.
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PMID:[Severe hypertriglyceridemia induced by tamoxifen]. 1006 74

Competition for respiration between substrates in animal tissues has been known for at least 80 years. The most important interaction, quantitatively is between glucose and fatty acids. The starting point in 1963 for the so called Glucose Fatty Acid Cycle was the realisation that the metabolic relationship between glucose and fatty acids is reciprocal and not dependent. Glucose provision promotes glucose oxidation and glucose and lipid storage, and inhibits fatty acid oxidation. Provision of free fatty acids promotes fatty acid oxidation and storage, inhibits glucose oxidation and may promote glucose storage if glycogen reserves are incomplete. This review is concerned predominantly with evidence in man in vivo. In the authors opinion the evidence for inhibitory effects of fatty acids on whole body glucose utilization ad oxidation (predominantly muscles) is decisive and enzyme mechanisms mediating these effects are well established. There is also much evidence that fatty acid oxidation inhibits glucose oxidation and stimulates glucose formation in liver and again enzyme mechanism are known. A permissive role for fatty acids in the insulin secretory response of islet beta-cells has now been firmly established and can be visualised as a mechanism to protect continuing provision of respiratory substrate. Longer term exposure of islet beta-cells to fatty acids impairs the insulin secretory response to glucose and mechanisms are known. There is compelling evidence that fatty acid oxidation may impair glucose oxidation in uncontrolled Type 1 and Type 2 diabetes, but no convincing evidence that fatty acids have a role in diminished glucose storage (glycogen deposition) in Type 2 diabetes. The inhibition of glucose storage which may follow prolonged elevation of plasma FFA in man and experimental animals is associated with glycogen repletion whereas the inhibition of glucose storage in Type 2 diabetes is associated with glycogen depletion. The precise role of fatty acids in disturbed carbohydrate metabolism in Type 2 diabetes is an area where future progress is confidently predicted.
Diabetes Metab Rev 1998 Dec
PMID:Regulatory interactions between lipids and carbohydrates: the glucose fatty acid cycle after 35 years. 1009 97

We determined whether habitual cigarette smoking alters insulin-stimulated glucose transport and GLUT4 protein expression in skeletal muscle. Vastus lateralis muscle was obtained from 10 habitual cigarette smokers and 10 control subjects using an open muscle biopsy procedure. Basal 3-O-methylglucose transport was twofold higher (P < 0.01) in muscle from habitual smokers (0.05 +/- 0.08 vs. 1.04 +/- 0.19 mumol ml-1 h-1; controls vs. smokers respectively). Insulin (600 pmol l-1) increased glucose transport 2.6-fold (P > 0.05) in muscle from control subjects, whereas no significant increase was noted in habitual smokers. Skeletal muscle GLUT4 protein expression was similar between the groups. FFA levels were elevated in the smokers (264 +/- 49 vs. 748 +/- 138 mumol l-1 for control subjects vs. smokers; P < 0.05), and serum triglyceride levels were increased in the smokers (0.9 +/- 0.2 vs. 2.3 +/- 0.6 mmol l-1 for control subjects vs. smokers; P < 0.05). Skeletal muscle carnitine palmitil (acyl) transferase activity was similar between the groups, indicating that FFA transport into the mitochondria was unaltered by cigarette smoking. In conclusion, cigarette smoking appears to have a profound effect on glucose transport in skeletal muscle. Basal glucose transport is markedly elevated, whereas insulin-stimulated glucose transport is impaired. These changes cannot be explained by altered protein expression of GLUT4, but may be related to increased serum FFA and triglyceride levels. These findings highlight the importance of identifying habitual cigarette smokers in studies aimed at assessing factors that lead to alterations in lipid and glucose homeostasis in people with non-insulin-dependent diabetes mellitus (NIDDM).
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PMID:Altered skeletal muscle glucose transport and blood lipid levels in habitual cigarette smokers. 1020 Aug 95

Prolonged exposure to elevated FFA levels has been shown to induce peripheral insulin resistance and to alter the beta-cell secretory response to glucose. To investigate the effects of FFAs on preproinsulin gene expression, we measured insulin release, cell content, and messenger RNA (mRNA) levels in rat islets after a 24-h exposure to 1 mM palmitate. Insulin release increased at all glucose concentrations studied; in contrast, preproinsulin mRNA levels were specifically reduced by palmitate at high glucose with a decrease in insulin stores, suggesting that palmitate inhibits the glucose-stimulated increase in preproinsulin gene expression. The mechanisms by which palmitate affects preproinsulin gene expression implicate both preproinsulin mRNA stability and transcription, as suggested by an actinomycin D decay assay, quantification of primary preproinsulin transcripts, and transient transfection experiments in Min6 cells. Metabolism of palmitate is not required to obtain these effects, inasmuch as they can be reproduced by 2-bromopalmitate. However, oleate and linoleate did not significantly influence preproinsulin mRNA levels. We conclude that insulin release and preproinsulin gene expression are not coordinately regulated by palmitate and that chronically elevated FFA levels may interfere with beta-cell function and be implicated in the development of noninsulin-dependent diabetes.
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PMID:Glucose-induced preproinsulin gene expression is inhibited by the free fatty acid palmitate. 1046 70

In lipoatrophic diabetes, a lack of fat is associated with insulin resistance and hyperglycemia. This is in striking contrast to the usual association of diabetes with obesity. To understand the underlying mechanisms, we transplanted adipose tissue into A-ZIP/F-1 mice, which have a severe form of lipoatrophic diabetes. Transplantation of wild-type fat reversed the hyperglycemia, dramatically lowered insulin levels, and improved muscle insulin sensitivity, demonstrating that the diabetes in A-ZIP/F-1 mice is caused by the lack of adipose tissue. All aspects of the A-ZIP/F-1 phenotype including hyperphagia, hepatic steatosis, and somatomegaly were either partially or completely reversed. However, the improvement in triglyceride and FFA levels was modest. Donor fat taken from parametrial and subcutaneous sites was equally effective in reversing the phenotype. The beneficial effects of transplantation were dose dependent and required near-physiological amounts of transplanted fat. Transplantation of genetically modified fat into A-ZIP/F-1 mice is a new and powerful technique for studying adipose physiology and the metabolic and endocrine communication between adipose tissue and the rest of the body.
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PMID:Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. 1067 52

The thiazolidinedione class of insulin-sensitizing, antidiabetic drugs interacts with peroxisome proliferator-activated receptor gamma (PPAR-gamma). To gain insight into the role of this nuclear receptor in insulin resistance and diabetes, we conducted metabolic studies in the PPAR-gamma gene knockout mouse model. Because homozygous PPAR-gamma-null mice die in development, we studied glucose metabolism in mice heterozygous for the mutation (PPAR-gamma(+/-) mice). We identified no statistically significant differences in body weight, basal glucose, insulin, or FFA levels between the wild-type (WT) and PPAR-gamma(+/-) groups. Nor was there a difference in glucose excursion between the groups of mice during oral glucose tolerance test, but insulin concentrations of the WT group were greater than those of the PPAR-gamma(+/-) group, and insulin-induced increase in glucose disposal rate was significantly increased in PPAR-gamma(+/-) mice. Likewise, the insulin-induced suppression of hepatic glucose production was significantly greater in the PPAR-gamma(+/-) mice than in the WT mice. Taken together, these results indicate that - counterintuitively - although pharmacological activation of PPAR-gamma improves insulin sensitivity, a similar effect is obtained by genetically reducing the expression levels of the receptor.
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PMID:Improved insulin-sensitivity in mice heterozygous for PPAR-gamma deficiency. 1067 54


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