Variation in the Phosphoinositide 3-Kinase Gamma Gene Affects Plasma HDL-Cholesterol without Modification of Metabolic or Inflammatory Markers.

Objective: Phosphoinositide 3-kinase γ (PI3Kγ) is a G-protein-coupled receptor-activated lipid kinase mainly expressed in leukocytes and cells of the cardiovascular system. PI3Kγ plays an important signaling role in inflammatory processes. Since subclinical inflammation is a hallmark of atherosclerosis, obesity-related insulin resistance, and pancreatic β-cell failure, we asked whether common genetic variation in the PI3Kγ gene (PIK3CG) contributes to body fat content/distribution, serum adipokine/cytokine concentrations, alterations in plasma lipid profiles, insulin sensitivity, insulin release, and glucose homeostasis.

Measuring Biological Age via Metabonomics: The Metabolic Age Score.

Chronological age is one of the most important risk factors for adverse clinical outcome. Still, two individuals at the same chronological age could have different biological aging states, leading to different individual risk profiles. Capturing this individual variance could constitute an even more powerful predictor enhancing prediction in age-related morbidity.

Tests for Anxiety-Related Behavior in Mice.

Phenotyping of inbred mouse strains and genetically modified mouse models for characteristics related to neuropsychiatric diseases includes assessing their anxiety-related behavior. A variety of tests have been developed to measure anxiety in laboratory rodents and these tests have been placed under scrutiny over the years concerning their validity. Here we describe the most widely used tests for anxiety in mice.

Changes in diabetes care indicators: findings from German National Health Interview and Examination Surveys 1997-1999 and 2008-2011.

Objectives: To investigate changes in type 2 diabetes care indicators over time in Germany.

Methods: Adults aged 45-79 years with type 2 diabetes were identified from two national health examination surveys conducted in 1997-1999 (GNHIES98, n=333) and in 2008-2011 (DEGS1, n=526). We examined diabetes care indicators including treatment and preventive targets (glycemic control, blood pressure (BP), total cholesterol (TC), smoking, weight reduction, sports activity), self-management and care process measures (glucose self-monitoring, holding a diabetes passport, annual foot and eye examination; statin use), and the presence of diabetes-specific complications (diabetic nephropathy, retinopathy, neuropathy, diabetic foot, amputations) and comorbid cardiovascular disease (CVD) or chronic kidney disease (CKD).

Aldehyde dehydrogenase activity is necessary for beta cell development and functionality in mice.

Aims/hypothesis: Pancreatic beta cells maintain glucose homeostasis and beta cell dysfunction is a major risk factor in developing diabetes. Therefore, understanding the developmental regulatory networks that define a fully functional beta cell is important for elucidating the genetic origins of the disease. Aldehyde dehydrogenase activity has been associated with stem/progenitor cells and we have previously shown that Aldh1b1 is specifically expressed in pancreas progenitor pools.

Changes in body weight and obesity status in German adults: results of seven population-based prospective studies.

Background/objectives: The objective of this study was to quantify body weight changes in German adult populations during the past decades.

Subjects/methods: Longitudinal analysis of seven cohort studies covering different age ranges between 18 and 83 years. Baseline examinations were between 1994 and 2007 and follow-up durations between 4.

Impaired insulin action in the human brain: causes and metabolic consequences.

Over the past few years, evidence has accumulated that the human brain is an insulin-sensitive organ. Insulin regulates activity in a limited number of specific brain areas that are important for memory, reward, eating behaviour and the regulation of whole-body metabolism. Accordingly, insulin in the brain modulates cognition, food intake and body weight as well as whole-body glucose, energy and lipid metabolism.

Incretin actions and consequences of incretin-based therapies: lessons from complementary animal models.

The two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP1), were discovered 45 and 30 years ago. Initially, only their insulinotropic effect on pancreatic β cells was known. Over the years, physiological and pharmacological effects of GIP and GLP1 in numerous extrapancreatic tissues were discovered which partially overlap, but may also be specific for GIP or GLP1 in certain target tissues.

Do dogs sense hypoglycaemia?

Aims: To summarize the current knowledge on the phenomenon of dogs, both trained and untrained, sensing hypoglycaemia and alerting their owners to it.

Methods: Electronic databases were searched for all types of articles reporting on untrained or trained 'diabetes alert' dogs. Articles published up until December 2014 in the English or German language were included.

Effects of dextromethorphan as add-on to sitagliptin on blood glucose and serum insulin concentrations in individuals with type 2 diabetes mellitus: a randomized, placebo-controlled, double-blinded, multiple crossover, single-dose clinical trial.

In this clinical trial, we investigated the blood glucose (BG)-lowering effects of 30, 60 and 90 mg dextromethorphan (DXM) as well as 100 mg sitagliptin alone versus combinations of DXM and sitagliptin during an oral glucose tolerance test (OGTT) in 20 men with T2DM. The combination of 60 mg DXM plus 100 mg sitagliptin was observed to have the strongest effect in the OGTT. It lowered maximum BG concentrations and increased the baseline-adjusted area under the curve for serum insulin concentrations in the first 30 min of the OGTT (mean ± standard deviation 240 ± 47 mg/dl and 8.

Fibroblast growth factor 21 is elevated in metabolically unhealthy obesity and affects lipid deposition, adipogenesis, and adipokine secretion of human abdominal subcutaneous adipocytes.

Objective: Serum concentrations of the hepatokine fibroblast growth factor (FGF) 21 are elevated in obesity, type-2 diabetes, and the metabolic syndrome. We asked whether FGF21 levels differ between subjects with metabolically healthy vs. unhealthy obesity (MHO vs.

Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy.

Aims: To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy.

Methods: The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation.

Distinct roles of β-cell mass and function during type 1 diabetes onset and remission.

Cure of type 1 diabetes (T1D) by immune intervention at disease onset depends on the restoration of insulin secretion by endogenous β-cells. However, little is known about the potential of β-cell mass and function to recover after autoimmune attack ablation. Using a longitudinal in vivo imaging approach, we show how functional status and mass of β-cells adapt in response to the onset and remission of T1D.

Important roles of the AKR1C2 and SRD5A1 enzymes in progesterone metabolism in endometrial cancer model cell lines.

Endometrial cancer is the most frequently diagnosed gynecological malignancy. It is associated with prolonged exposure to estrogens that is unopposed by progesterone, whereby enhanced metabolism of progesterone may decrease its protective effects, as it can deprive progesterone receptors of their active ligand. Furthermore, the 5α-pregnane metabolites formed can stimulate proliferation and may thus contribute to carcinogenesis.

Antihyperglycaemic therapies and cancer risk.

Aims: This review is aimed at highlighting the potential mitogenic/tumour growth-promoting or antimitogenic/tumour growth-inhibiting effects of the main antihyperglycaemic drug classes.

Methods: We review and discuss the most current studies evaluating the association between antidiabetic medications used in clinical practice and malignancies as described so far.

Results: Metformin seems to be the only antidiabetic drug to exert protective effects both on monotherapy and also when combined with other oral antidiabetic drugs or insulins in several site-specific cancers.

Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

Aims/hypothesis: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs) in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans.

Methods: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707).

Genetic variants in MTNR1B affecting insulin secretion.

The incidence of type 2 diabetes mellitus has markedly increased worldwide over the past decades. Pancreatic beta-cell dysfunction as well as central and peripheral insulin resistance appears to be elementary features in the pathophysiology of type 2 diabetes mellitus. Major environmental conditions predisposing to the development of type 2 diabetes are excessive food intake and sedentary life-style on the background of a genetic predisposition.

Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion.

Background: Prohormone convertase 1 is involved in maturation of peptides. Rare mutations in gene PCSK1, encoding this enzyme, cause childhood obesity and abnormal glucose homeostasis with elevated proinsulin concentrations. Common single nucleotide polymorphisms (SNPs) within this gene, rs6232 and rs6235, are associated with obesity.