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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The nutritional value of glycerol-1,2,3-tris(methylsuccinate), a novel ester of succinic acid with high insulinotropic efficiency both in vitro and in vivo, was assessed in both fed and starved rats. The infusion of the ester, given in a daily amount (1.2 micromol. g body wt-1) well in excess of what could result from its repeated intravenous administration as an insulinotropic agent in non-insulin-dependent diabetes (0.07 micromol. g body wt-1 for each administration), failed to prevent the fall in body weight, liver and muscle glycogen contents, and plasma d-glucose or insulin concentration, as well as the increase in plasma free fatty acid and beta-hydroxybutyrate concentrations caused by starvation. The sole indications that the ester may serve, to a limited extent, as an alternative nutrient in starved rats consisted in a somewhat higher weight of both liver and paraovarian adipose tissue and somewhat higher activity of liver glucokinase in rats receiving the ester than in animals infused with saline. The low nutritional value of this ester thus answers the objection of its possible role as an extrapancreatic nutrient or gluconeogenic precursor in the perspective of its use as an insulinotropic tool in type 2 diabetes.
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PMID:Assessment of the nutritional value of glycerol-1,2, 3-tris(methylsuccinate) in fed and starved rats. 1038 33

In the genesis and development of type 2 diabetes in the great majority of subjects the contemporary lifestyle characterized by inadequate physical activity and an excessive energy intake is of basic importance. The majority of abnormalities and defects revealed by laboratory tests is probably secondary and caused by the above mentioned factors. Contemporary views of the etiopathogenesis of the disease are demotivating for patients: if the cause of their disease were an inborn disorder at the level of transmission of a signal on membranes then probably nothing else can be done than to take prescribed drugs. If the mistake involves the lifestyle, the latter can be changed and the disease avoided. Any medicamentous treatment is associated with the risk of undesirable effects--the complication of hyperinsulinism in treatment with sulphonyl urea derivatives and insulin or lactate acidosis after treatment with biguanides. This risk is not influenced by early prevention: dietary restraint and adequate physical exercise. Diabetes type 2 and 1--despite the common sign of hyperglycaemia--are characterized by a fundamental difference: (not influenced by treatment) DM type 1 is characterized by enhanced catabolic processes, starvation at the cellular level. Type 2 is characterized by enhanced anabolic processes, excessive amounts of nutrients in cells. The authors submit recommendations which respect the secondary character of deviations for the development of DM 2 which can be detected by laboratory methods: The following are the basic etiopathogenetic mechanism for the development of DM 2: 1. Chronic excessive intake and inadequate output of energy a) increased nutrient supply to the liver with secondary increase of gluconeogenesis in the liver, b) chronic increased supply of glucose to peripheral tissues, in particular muscles and adipose tissue, inadequate physical exercise, with secondary restriction of nutrient supplies to these tissues. 2. Secondary affection of insulin secretion in the islets of Langerhans in the pancreas.
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PMID:[Etiopathogenesis of type 2 diabetes mellitus]. 1095 50

A key feature of type 2 diabetes is impairment in the stimulation of glycogen synthesis in skeletal muscle by insulin. Glycogen synthesis and the activity of the enzyme glycogen synthase (GS) have been studied in human myoblasts in culture under a variety of experimental conditions. Incubation in the absence of glucose for up to 6 h caused an approximately 50% decrease in glycogen content, which was associated with a small decrease in the fractional activity of GS. Subsequent reincubation with physiological concentrations of glucose led to a dramatic increase in the rate of glycogen synthesis and in the fractional activity of GS, an effect which was both time- and glucose concentration-dependent and essentially additive with the effects of insulin. This effect was seen only after glycogen depletion. Inhibitors of signaling pathways involved in the stimulation of glycogen synthesis by insulin were without significant effect on the stimulatory action of glucose. These results indicate that at least two distinct mechanisms exist to stimulate glycogen synthesis in human muscle: one acting in response to insulin and the other acting in response to glucose after glycogen depletion, such as that which results from exercise or starvation.
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PMID:Control of glycogen synthesis by glucose, glycogen, and insulin in cultured human muscle cells. 1128 34

Adipose tissue glyceroneogenesis generates glycerol 3-phosphate, which could be used for fatty acid esterification during starvation. To determine whether increased glyceroneogenesis leads to increased fat mass and to explore the role of obesity in the development of insulin resistance, we overexpressed PEPCK, a regulatory enzyme of glyceroneogenesis in adipose tissue. Transgenic mice showed a chronic increase in PEPCK activity, which led to increased glyceroneogenesis, re-esterification of free fatty acids (FFAs), increased adipocyte size and fat mass, and higher body weight. In spite of increased fat mass, transgenic mice showed decreased circulating FFAs and normal leptin levels. Moreover, glucose tolerance and whole-body insulin sensitivity were preserved. Skeletal muscle basal and insulin-stimulated glucose uptake and glycogen content were not affected, suggesting that skeletal muscle insulin sensitivity is normal in transgenic obese mice. Our results indicate the key role of PEPCK in the control of FFA re-esterification in adipose tissue and, thus, the contribution of glyceroneogenesis to fat accumulation. Moreover, they suggest that higher fat mass without increased circulating FFAs does not lead to insulin resistance or type 2 diabetes in these mice.
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PMID:Increased fatty acid re-esterification by PEPCK overexpression in adipose tissue leads to obesity without insulin resistance. 1187 59

The "thrifty" genotype and phenotype that save energy are detrimental to the health of people living in affluent societies. Individual differences in energy metabolism are caused primarily by single nucleotide polymorphisms (SNPs), some of which promote the development of obesity/type 2 diabetes mellitus. In this review, four major questions are addressed: (1) Why did regional differences in energy metabolism develop during evolution? (2) How do genes respond to starvation and affluence? (3) Which SNPs correspond to the hypothetical "thrifty genes"? (4) How can we cope with disease susceptibility caused by the "thrifty" SNPs? We examined mtDNA and genes for energy metabolism in people who live in several parts of Asia and the Pacific islands. We included 14 genes, and the SNP frequencies of PPAR gamma 2, LEPR, and UCP3-p and some other genes differ significantly between Mongoloids and Caucasoids. These differences in SNPs may have been caused by natural selection depending on the types of agriculture practiced in different regions. Interventions to counteract the adverse effects of "thrifty" SNPs have been partially effective.
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PMID:Single nucleotide polymorphisms of thrifty genes for energy metabolism: evolutionary origins and prospects for intervention to prevent obesity-related diseases. 1215 Sep 34

The regulation of fat and glucose metabolism in the liver is controlled primarily by insulin and glucagon. Changes in the circulating concentrations of these hormones signal fed or starvation states and elicit counter-regulatory responses that maintain normoglycaemia. Here we show that in normal mice, plasma insulin inhibits the forkhead transcription factor Foxa2 by nuclear exclusion and that in the fasted (low insulin) state Foxa2 activates transcriptional programmes of lipid metabolism and ketogenesis. In insulin-resistant or hyperinsulinaemic mice, Foxa2 is inactive and permanently located in the cytoplasm of hepatocytes. In these mice, adenoviral expression of Foxa2T156A, a nuclear, constitutively active Foxa2 that cannot be inhibited by insulin, decreases hepatic triglyceride content, increases hepatic insulin sensitivity, reduces glucose production, normalizes plasma glucose and significantly lowers plasma insulin. These changes are associated with increased expression of genes encoding enzymes of fatty acid oxidation, ketogenesis and glycolysis. Chronic hyperinsulinaemia in insulin-resistant syndromes results in the cytoplasmic localization and inactivation of Foxa2, thereby promoting lipid accumulation and insulin resistance in the liver. Pharmacological intervention to inhibit phosphorylation of Foxa2 may be an effective treatment for type 2 diabetes.
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PMID:Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. 1561 40

Attention was recently drawn to differences in the fatty acid pattern of liver phospholipids and triglycerides in animal models of type 1 and type 2 diabetes. The present study extends this knowledge to epididymal or parametrial adipose tissue lipids. The fatty acid pattern of such lipids was established in four fed female normal rats, four overnight fasted female normal rats, six fed female rats rendered diabetic by an injection of streptozotocin 3 days before sacrifice (STZ rats), and four female and four male Goto-Kakizaki rats (GK rats) also examined in the fed or fasted state. In addition to the fasting-induced and diabetes-related changes in plasma D-glucose and insulin concentrations, differences in either the weight percentage of fatty acids or the paired ratio between distinct fatty acids were often encountered. For instance, in the GK rats, gender differences were observed in the weight percentage of C18:2omega6, as well as C18:2omega6/C18:3omega6, C18:3omega6/C20:4omega6, C20:5omega3/C22:5omega3 and C22:5omega3/C22:6omega3 ratios. When compared to normal rats, the activity of Delta9-desaturase was markedly increased in GK rats and, to a lesser extent, in STZ rats. Starvation also increased to some extent the activity of Delta9-desaturase. The relative content of C22:6omega3 was also higher in diabetic than in normal rats. Further differences between GK and STZ rats concerned the generation of C18:3omega6 from C18:2omega6, C20:4omega6 from C18:3omega6, and C20:5omega3 from C18:3omega3. Several differences found in the adipose tissue of GK versus STZ rats were reminiscent of those recently identified in the liver triglycerides of these two types of diabetic animals, suggesting a common regulatory mechanism, possibly linked to the higher insulinemia of GK rats versus STZ rats.
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PMID:Fatty acid content and pattern of epididymal and parametrial adipose tissue lipids in streptozotocin (type 1) and Goto-Kakizaki (type 2) diabetic rats. 1708 31

The Formando Nuestro Futuro/Shaping our Future project (herewith, Formando) is a community-based participative research (CBPR) focused on type 2 diabetes. It was conceptualized and designed by a team of university-based researchers and community health workers (promotores). This article describes the process of establishing a CBPR project such as Formando and the most current results from that project. The Formando project is an example of health-focused advocacy with the Mexican agricultural workers in Southeast (SE) Idaho. To date, 172 qualitative interviews on participants' knowledge about type 2 diabetes have been carried out with farmworker women and their families. Biometric data (heights, weights, blood pressures and fasting blood glucoses) were obtained from participants. Fieldnotes, focus group discussions and key informants were used to triangulate findings. Significant quantitative findings include that age was significantly associated with Body Mass Index (BMI) (p < 0.001, Spearman Correlation < 0.001) and with elevated fasting blood glucose (p < 0.001, Spearman Correlation < 0.001). The qualitative interviews were thematically analyzed. Key themes associated with type 2 diabetes in this community were the connection between thinness and vanity, dieting and starvation and the onset of diabetes as a result of, what social scientists call, structural violence within the immigrants' daily lives. We conclude that long-term commitment to using the CBPR approach in these Mexican agricultural communities is an effective way to engage in health research and to establish real and meaningful dialogue with community members.
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PMID:Using participatory research to build an effective type 2 diabetes intervention: the process of advocacy among female Hispanic farmworkers and their families in Southeast Idaho. 1713 90

Chronic inflammation contributes to vascular insulin resistance and endothelial dysfunction. Systemic infusion of TNF-alpha abrogates insulin's action to enhance skeletal muscle microvascular perfusion. In skeletal muscle TNF-alpha induces insulin resistance via the p38 MAPK pathway. To examine whether p38 MAPK also regulates TNF-alpha-induced vascular insulin resistance, bovine aortic endothelial cells (bAECs) were incubated+/-TNF-alpha (5 ng/ml) for 6 h in the presence or absence of SB203580 (p38 MAPK specific inhibitor, 10 microM) after serum starvation for 10 h. For the last 30 min, cells were treated+/-1 nM insulin, and insulin receptor substrate (IRS)-1, Akt, endothelial nitric oxide synthase (eNOS), p38 MAPK, ERK1/2, c-Jun N-terminal kinase, and AMP-activated protein kinase (AMPK) phosphorylation, and eNOS activity were measured. TNF-alpha increased p38 MAPK phosphorylation, potently stimulated IRS-1 serine phosphorylation, and blunted insulin-stimulated IRS-1 tyrosine and Akt phosphorylation and eNOS activity. TNF-alpha also potently stimulated the phosphorylation of ERK1/2 and AMPK. Treatment with SB203580 decreased p38 MAPK phosphorylation back to the baseline and restored insulin sensitivity of IRS-1 tyrosine and Akt phosphorylation and eNOS activity in TNF-alpha-treated bAECs without affecting TNF-alpha-induced ERK1/2 and AMPK phosphorylation. We conclude that in cultured bAECs, TNF-alpha induces insulin resistance in the phosphatidylinositol 3-kinase/Akt/eNOS pathway via a p38 MAPK-dependent mechanism and enhances ERK1/2 and AMPK phosphorylation independent of the p38 MAPK pathway. This differential modulation of TNF-alpha's actions by p38 MAPK suggests that p38 MAPK plays a key role in TNF-alpha-mediated vascular insulin resistance and may contribute to the generalized endothelial dysfunction seen in type 2 diabetes mellitus and the cardiometabolic syndrome.
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PMID:Tumor necrosis factor-alpha induces insulin resistance in endothelial cells via a p38 mitogen-activated protein kinase-dependent pathway. 1744 86

The incidence of the metabolic syndrome, type 2 diabetes and cardio- and cerebrovascular disease is increasing in the Western world. The adipocyte derived protein adiponectin is thought to have a protective role against these conditions. But why is it so? Is it reasonable to believe that we have adiponectin to gain protection from welfare related diseases? Humans have had a far deadlier foe throughout history than obesity and sedentariness and that is starvation. During starvation, the body is catabolic in order to provide fuel. Catabolism is also seen in patients with advanced cardiac or renal failure, type 1 diabetes and anorexia. These subjects have higher adiponectin levels than controls. In this article, I will put forward the hypothesis that the adiponectin system evolved in order to help us to survive periods of malnourishment.
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PMID:Adiponectin: saving the starved and the overfed. 1750 73


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