Diabetologia

http://link.springer.com/journal/125

List of Papers (Total 8,147)

Effects of angiotensin II on insulin receptor binding and mRNA levels in normal and diabetic rats

Summary Both the density and level of mRNA encoding insulin receptors in the kidney are inversely related to the dietary sodium content, suggesting a feedback mechanism that limits the insulin-induced sodium retention when extracellular fluid volume is expanded. Because angiotensin II affects tissue sensitivity to insulin in humans, we investigated whether angiotensin II affects...

Microdialysis techniques in the study of brain and skeletal muscle

Traditionally, plasma measurements have been used to monitor metabolic events and the actions of hormones that are actually taking place within tissue beds that are anatomically separated from the vascular compartment. It is generally assumed that the extracellular fluid (ECF) within metabolically active tissues is composed of substrates and hormones in concentrations that...

The lymphopenia (lyp ) gene controls the intrathymic cytokine ratio in congenic BioBreeding rats

The lymphopenia gene (lyp ) on rat chromosome 4 is closely linked to autoimmune diabetes in the BioBreeding (BB) rat. Lyp controls the number of peripheral lymphocytes by reducing T cells of the RT6 + phenotype by almost 90 %. Following nine cycles of marker-assisted cross-intercross breeding we have developed congenic lyp/lyp, lyp/ + and + / + (wildtype) rats on the background...

Effect of feeding, fasting, and diabetes on liver glycogen synthase activity, protein, and mRNA in rats

Hepatic glycogen synthase activity is increased in diabetic animals. However, the relationship between enzymic activity, enzyme protein mass, and mRNA abundance has not been well characterized. In the present study, these relationships were determined in 3- and 8-day diabetic, fed and fasted rats. The results were compared to data obtained in normal fed and fasted animals. In...

Modifications in the B10 and B26–30 regions of the B chain of human insulin alter affinity for the human IGF-I receptor more than for the insulin receptor

Inversion of the natural sequence of the B chain of human insulin (HI) from ProB28LysB29 to LysB28ProB29 generates an insulin analogue with reduced tendency to self-associate. Since this substitution increases the homology of insulin to insulin-like growth factor-I (IGF-I), we have examined the affinity of a series of insulin analogues with the general modified structure...

Signal transduction mechanisms in nutrient-induced insulin secretion

Summary The knowledge of the mechanism whereby glucose and other fuel stimuli promote the release of insulin by the pancreatic beta cell remains fragmentary. The closure of metabolically sensitive K+ channels and a rise in cytosolic free Ca 2+ are key features of beta-cell metabolic signal transduction. However, these two signalling events do not account for the dose dependence...

Mitogenic properties of insulin and insulin analogues mediated by the insulin receptor

Insulin has traditionally been considered as a hormone essential for metabolic regulation, while the insulin-like growth factors (IGF-I and IGF-II) are postulated to be more specifically involved in growth regulation. The conventional wisdom is that they share each other's effects only at high concentrations, due to their weak affinity for the heterologous receptor. We discuss...

Control of PHAS-I phosphorylation in 3T3-L1 adipocytes: effects of inhibiting protein phosphatases and the p70S6K signalling pathway

PHAS-I is a recently discovered regulator of translation initiation. Non-phosphorylated PHAS-I binds and inhibits eukaryotic initiation factor-4E, the mRNA cap-binding protein that mediates a rate-limiting step in translation initiation. When PHAS-I is phosphorylated in response to insulin, the PHAS-I/eukaryotic initiation factor-4E complex dissociates. The present study was...

Relationship between insulin-mediated glucose disposal and regulation of plasma and adipose tissue lipoprotein lipase

The relationship between insulin-mediated glucose disposal and fasting insulin and triglyceride (TG) concentrations, plasma post-heparin lipoprotein lipase (PH-LPL) activity and mass, and adipose tissue LPL activity, mass, and mRNA content was defined in 19 non-diabetic men. Insulin-mediated glucose uptake [as assessed by determining the steady-state plasma glucose (SSPG...

Protein kinase C isoforms β 1 and β 2 inhibit the tyrosine kinase activity of the insulin receptor

Downregulation of insulin receptor tyrosine kinase (IRK) activity yields to impaired insulin signalling and contributes to the pathogenesis of cellular insulin resistance. Activation of protein kinase C (PKC) by different agents is associated with an inhibition of IRK activity in various cell types. There is evidence that this effect on IRK activity might be mediated through...

No effect of the Trp64Arg β3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue

A Trp64Arg variant in the human β 3-adrenoceptor is associated with earlier onset of non-insulin-dependent diabetes mellitus and obesity in several populations. The present study investigated in vivo lipolysis in individuals homozygous for the ’variant' allele coding for arginine (Arg) in position 64 of the β 3-adrenoceptor or homozygous for the ’wild type' tryptophan (Trp...

Prevalence of NIDDM and impaired glucose tolerance in a rural and an urban population in Cameroon

Summary The adoption of Western lifestyles is known to lead to increasing prevalence of non-insulin-dependent diabetes mellitus in Africa, yet epidemiological studies using standardised methods are rare. The prevalence of diabetes and impaired glucose tolerance was determined in a rural and an urban community in Cameroon using the 75-g oral glucose tolerance test and the World...

Chronic leptin treatment does not prevent the development of obesity in transgenic mice with brown fat deficiency

With the exception of ob/ob mice, circulating plasma leptin is elevated in all other obese rodents as well as in obese humans, suggesting that leptin resistance rather than leptin deficiency is a characteristic feature of obesity. The exact molecular mechanisms leading to leptin resistance and the applicability of exogenous leptin to overcome resistance to the anorectic effect of...

Increased epidermal growth factor in experimental diabetes related kidney growth in rats

Renal enlargement is a characteristic feature of human and experimental diabetes mellitus that may be predictive of subsequent nephropathy. In the streptozotocin diabetic rat kidney growth rapidly follows the induction of experimental diabetes but the mechanisms responsible for this growth are poorly understood. Epidermal growth factor (EGF) is a potent mitogen for renal tubular...

Altered immunoreactivity of islet amyloid polypeptide (IAPP) may reflect major modifications of the IAPP molecule in amyloidogenesis

We have developed a mouse monoclonal antibody against rat/mouse islet amyloid polypeptide (IAPP). The antibody recognises an epitope in the N-terminal part of the molecule, which is conserved between different species. The antibody immunohistochemically labelled beta cells in normal islets of most different mammalian species including man and in one avian species. Previous...

The relationship between accumulation of advanced glycation end products and expression of vascular endothelial growth factor in human diabetic retinas

Both advanced glycation end products and vascular endothelial growth factor are believed to play a role in the pathogenesis of diabetic retinopathy. It is known that vascular endothelial growth factor causes retinal neovascularization and a breakdown of the blood-retinal barrier; how advanced glycation end products affect the retina, however, remains largely unclear. The...

Renal glucose production and utilization: new aspects in humans

According to current textbook wisdom the liver is the exclusive site of glucose production in humans in the postabsorptive state. Although many animal and in vitro data have documented that the kidney is capable of gluconeogenesis, production of glucose by the human kidney in the postabsorptive state has generally been regarded as negligible. This traditional view is based on net...

Engineered cell lines for insulin replacement in diabetes: current status and future prospects

The recently completed diabetes complications and control trial has highlighted the need for improvement of insulin delivery systems for treatment of insulin-dependent diabetes mellitus. Despite steady improvement in methods for islet and whole pancreas transplantation over the past three decades, the broad-scale applicability of these approaches remains uncertain due in part to...

Advances and prospects in glucose assay technology

The evolution of glucose assay methods has been central to the development of present therapies for diabetes mellitus. However, new blood glucose assay capabilities, such as convenient and truly continuous monitoring, are now needed to foster a new era of close blood glucose control. The principles and present status of glucose sensors being developed that may fill these...

Are presently available insulin analogues clinically beneficial?

A number of insulin analogues have been developed by genetic engineering in order to improve the possibilities of substituting prandial and basal insulin requirements in diabetic patients by subcutaneous injection. For some short acting insulin analogues, in particular for [Lys(B28),Pro(B29)]-human insulin, preclinical and clinical trials have been performed. Despite the...

Intensive insulin therapy in clinical practice

Achieving optimal blood glucose control, without an unacceptable rate of hypoglycaemia or unacceptable restrictions on lifestyle, is not simple with presently available insulin preparations and monitoring tools. There is considerable evidence that achieved control is relatively independent of the means or frequency of insulin delivery provided at least two injections per day are...

Hypoglycaemia in diabetes mellitus – protecting the brain

The human brain generally uses glucose as its principal metabolic fuel but cerebral metabolism and function during hypoglycaemia can be supported by a variety of substrates. Different brain regions may vary in this. The brain's ability to sense a falling blood glucose concentration and initiate a protective response varies according to prior glycaemic experience. The brain's...

The new era of biotech insulin analogues

Many of the structural properties of insulin have evolved in response to the requirements of biosynthesis, processing, transport and storage in the pancreatic beta cells, properties that are not necessary for the biological action of the hormone. It is therefore not surprising that wild-type insulin has far from optimal characteristics for replacement therapy. For example, native...