Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The liver is mainly responsible for maintaining normal concentrations of blood glucose by its ability to store glucose as glycogen and to produce glucose from glycogen breakdown or gluconeogenic precursors. During the last decade, new techniques have made it possible to gain further insight into the turnover of hepatic glucose and glycogen in humans. Hepatic glycogen varies from approximately 200 to approximately 450 mM between overnight fasted and postprandial conditions. Patients with type-1 diabetes (T1DM), type 2 diabetes (T2DM) or partial agenesis of the pancreas exhibit increased endogenous glucose production and synthesize only 25-45% of hepatic glycogen compared with non-diabetic humans. This defect can be partly restored in T1DM by combined long- and short-term optimized treatment with insulin. In T2DM, increased gluconeogenesis was identified as the main cause of elevated glucose production and fasting hyperglycaemia. These patients also exhibit augmented intracellular lipid accumulation which could hint at a link between deranged glucose and lipid metabolism in insulin-resistant states.
Best Pract Res Clin Endocrinol Metab 2003 Sep
PMID:Hepatic glucose metabolism in humans--its role in health and disease. 1296 91

Obesity is commonly associated with elevated plasma levels of free fatty acids (FFAs). High levels of FFA have emerged as a major link between obesity and insulin resistance/type 2 diabetes (T2DM). Thus, acute and chronic elevations of plasma FFAs produce insulin resistance in skeletal muscle and liver. In skeletal muscle, FFA-induced insulin resistance is associated with accumulation of intramyocellular triglyceride and diacylglycerol, and with activation of protein kinase C (the beta and delta isoforms). It is suggested that FFAs interfere with insulin signalling via PKC-induced serine phosphorylation of the insulin receptor substrate-1. In the liver, FFAs cause insulin resistance by interfering with insulin suppression of glycogenolysis. In beta-cells, FFAs potentiate glucose-stimulated insulin secretion acutely and chronically. It is postulated that this prevents the development of T2DM in most (>80%) obese insulin-resistant people who have FFA-mediated insulin resistance. Elevated levels of FFA also seem to activate a pro-inflammatory and pro-atherogenic pathway (the IkappaB/NFkappaB pathway) and may be responsible, at least in part, for the increase in atherosclerotic vascular disease seen in patients with T2DM. As increased plasma levels account for up to 50% of insulin resistance in obese patients with T2DM, lowering of plasma FFAs could be a new and promising approach to the treatment of T2DM.
Best Pract Res Clin Endocrinol Metab 2003 Sep
PMID:Nutritional effects of fat on carbohydrate metabolism. 1296 93

To understand the mechanism of insulin signalling and insulin resistance in the development of type 2 diabetes, it is necessary to elucidate the role of insulin and related signal molecules in normal cellular development and functions. A technique for addressing this problem, which is growing more and more important, is the generation and characterization of knockout animal models; such models allow in vivo study of the effects of a lack of a certain gene product, for example, a hormone or intracellular signalling molecule, on the viability, development and physiology of the animal. Besides the conventional form of knockout-which abolishes expression of the gene of interest in every cell of the body and during embryonic development-more recent technology permits the selective inactivation of genes in a tissue-specific and even time-controlled manner. With these techniques, it has become possible not only to examine the function of genes whose conventional inactivation would be lethal for the animal, but also to examine the specific functions that these genes have in certain tissues or at certain developmental stages. Here, we review the phenotype of mice resulting from both conventional and conditional inactivation of molecules in the insulin signalling cascade; this work has led to novel concepts in the understanding of insulin action and the development of insulin resistance.
Best Pract Res Clin Endocrinol Metab 2003 Sep
PMID:Genetic manipulation of the insulin signalling cascade in mice--potential insight into the pathomechanism of type 2 diabetes. 1296 95

Based on our investigations in first-degree relatives, in twins in general, and in monozygotic twins discordant for type 2 diabetes, we have studied the inheritance of glucose intolerance, insulin resistance and insulin secretion in order to evaluate the role of genes versus environment in the development of type 2 diabetes. Insulin resistance in type 2 diabetes is mainly linked to glucose disposal in skeletal muscle, i.e. reduced glycogen synthesis. In order to investigate the genetic component responsible for the reduced glycogen synthase activity and reduced glucose transport, we also investigated cultured myotubes based on in vivo skeletal muscle biopsies. The results obtained in our own studies are discussed in comparison with the international literature. We conclude that both genetic and environmental factors play a role in the development of type 2 diabetes (hyperglycaemia), and that only subjects who are genetically disposed to insulin resistance and who possess beta-cells which are unable to compensate for the degree of insulin resistance seem to develop type 2 diabetes. Variables of two gene alleles disposing to insulin resistance have been identified, and their role is discussed. The most important environmental factor seems to be obesity, but intrauterine malnutrition also plays a role. The cellular mechanism responsible for obesity/lipid-induced diabetes mellitus is discussed with specific emphasis on the role of accumulation of long-chain AcylCoA and triglycerides in liver, muscle and beta-cells.
Best Pract Res Clin Endocrinol Metab 2003 Sep
PMID:Metabolic and genetic influence on glucose metabolism in type 2 diabetic subjects--experiences from relatives and twin studies. 1296 96

The prevalence of type 2 diabetes mellitus is rising rapidly in all developed countries, particularly in the growing population of persons >50 years of age. As a dangerous consequence, this is accompanied by a proportionate increase in the incidence of chronic renal disease. Evidence-based medicine has shown that tight blood glucose control can delay the onset and retard the progression of diabetic complications, and while it is a challenge to closely manage the complexity of diabetes, it is more difficult to effectively treat the multiple associated comorbidities that develop. Best practice guidelines support early intervention and aggressive treatment of hypertension, hyperglycaemia, proteinuria, hypercholesterolemia, and anaemia. To date, guideline-based management has been proven to be difficult. This article describes the concept of the IRIDIEM studies. The objective of these studies is to endorse and facilitate the use of current best practice guidelines for the management of frequent comorbid diseases and established risk factors in the treatment of type 2 diabetes associated with chronic kidney disease. Additionally, IRIDIEM will assess the impact of this improved disease management model on the progression of chronic kidney disease that can result from electronically prompting clinicians with evidence-based treatment advice.
 ...
PMID:Individualized risk management in diabetics: how to implement best practice guidelines--design and concept of the IRIDIEM studies. 1511 29

Polycystic ovary syndrome (PCOS) is a common clinical and metabolic condition in women of reproductive age. It is associated with short-term reproductive and long-term metabolic dysfunction. Treatment has traditionally focused on fertility and hormonal therapy. However, general obesity, central obesity and insulin resistance are strongly implicated in its aetiology and improving these factors has proved highly successful in some clinical situations, reducing the need for costly assisted reproduction. A low-fat, high-carbohydrate diet is thought to improve insulin sensitivity, aid in weight loss and reduction of metabolic and reproductive symptoms and improve the long-term maintenance of a reduced weight. However, there has been recent community interest in adopting a protocol advocating a moderate increase in dietary protein for improving weight loss and PCOS symptoms. Altering the glycaemic index of the diet has also received considerable attention as a regime for promoting satiety and reducing metabolic risk factors for type 2 diabetes mellitus and cardiovascular disease. Exercise and other lifestyle changes are essential for altering the short- and long-term effects of PCOS. It is vital that the efficacy of these strategies is assessed so that accurate medical and dietetic advice can be given both to patients and to the health-care community.
Best Pract Res Clin Obstet Gynaecol 2004 Oct
PMID:Understanding and managing disturbances in insulin metabolism and body weight in women with polycystic ovary syndrome. 1538 Jan 43

The 42 amino acid polypeptide glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide (GIP) is released from intestinal K-cells in response to nutrient ingestion. Based on animal studies, the peptide was initially assumed to act as an endogenous inhibitor of gastric acid secretion. Later it was found that GIP is capable of augmenting glucose-stimulated insulin secretion, and subsequent studies provided evidence that, in humans, the peptide predominantly acts as an incretin hormone. A role for GIP in the regulation of lipid homeostasis and in the development of obesity has been inferred from different animal studies. While GIP strongly stimulates insulin release in healthy humans, the peptide has almost completely lost its insulinotropic effect in patients with type 2 diabetes. This is different from the actions of glucagon-like peptide 1, which stimulates insulin secretion even in the later stages of type 2 diabetes. This suggests that a diminished insulinotropic effect of GIP may contribute to the pathogenesis of type 2 diabetes. This review will summarize the actions of GIP in human physiology and discuss its role in the pathogenesis of type 2 diabetes, as well as the therapeutic options derived from these findings.
Best Pract Res Clin Endocrinol Metab 2004 Dec
PMID:Clinical endocrinology and metabolism. Glucose-dependent insulinotropic polypeptide/gastric inhibitory polypeptide. 1553 77

At the beginning of the 21st Century, obesity has become the leading metabolic disease in the World. So much so, that the World Health Organisation refers to obesity as the global epidemic. In fact, obesity is a common disease affecting not only affluent societies but also developing countries. Currently 300 million people can be considered as obese and, due to the rising trend in obesity prevalence, this figure could double by year 2025 if no action is taken against this threat. In terms of health impairment, the importance of obesity lies in the fact that, besides being a disease in itself, it is a risk for many other diseases, mainly from the metabolic and cardiovascular area. Among these, type 2 diabetes, dyslipemia, hyperuricemia, arterial hypertension and cardiovascular disease are the most frequent. Also, respiratory diseases such as obesity hypoventilation syndrome and obstructive sleep apnoea syndrome are strongly associated with obesity.
Best Pract Res Clin Gastroenterol 2004 Dec
PMID:Obesity: epidemiology and clinical aspects. 1556 43

Childhood obesity is prevalent and linked to the development of Type 2 diabetes mellitus (DM) and poor bone health. Some PUFA enhance bone mass and thus may improve bone health in obese children. The study objective was to determine the effects of dietary (n-6) compared with (n-3) essential PUFA and long-chain PUFA (LCPUFA) on bone in an obese and insulin-resistant state. Male fa/fa (n = 48) and lean Zucker rats (n = 48) were fed diets containing safflower oil [SO, high (n-6) PUFA], flaxseed oil [FXO, high (n-3) PUFA], or menhaden oil [MO, high (n-3) LCPUFA] for 9 wk. Measurements included the following: femur bone area (BA), mineral content (BMC), density (BMD), morphometry and ex vivo release of prostaglandin E(2) (PGE(2)); plasma osteocalcin and C-terminal telopeptides of type I collagen. Differences among groups were detected using 2-way ANOVA. Genotype effects in the fa/fa rats included lower femoral weight, length, BA, and BMC, as well as femoral head and proximal epiphysis widths compared with the lean rats, but BMD was not affected. Femur BA, BMC, and BMD did not differ among the dietary groups, but diaphysis width was elevated in the MO group and PGE(2) release was reduced by the FXO and MO diets. No genotype x diet interactions were observed. These data indicate that the fa/fa Zucker rat is at risk for low bone mass and that dietary (n-3) FA effectively reduce PGE(2) release. Whether reduced PGE(2) will support optimal peak bone mass during childhood and conserve bone mass with aging warrants investigation.
 ...
PMID:(n-3) fatty acids reduce the release of prostaglandin E2 from bone but do not affect bone mass in obese (fa/fa) and lean Zucker rats. 1573 84

Diabetic thoracic polyradiculopathy usually causes severe, chronic abdominal pain in patients with type 2 diabetes of variable duration. Other diabetic complications, weight loss and paretic abdominal wall protrusion are common. Sensory, motor and autonomic functions are affected. The diagnosis can be made from the characteristic history, physical examination findings, paraspinal electromyography, and other procedures. The differential diagnosis includes postherpetic neuralgia, abdominal wall pain, malignancy, and other spinal disorders. The pathology appears to be immune-mediated neurovasculitis resulting in ischemic injury. Traditional therapy is symptomatic, but recent pathological findings and clinical experience suggest that immunotherapy may be effective.
Best Pract Res Clin Gastroenterol 2005 Apr
PMID:Diabetic thoracic polyradiculopathy. 1583 93


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