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Karlsruhe, Germany

He H.,Chongqing Medical University | Yang D.,Chongqing Medical University | Ma L.,Chongqing Medical University | Luo Z.,Chongqing Medical University | And 7 more authors.
Hypertension | Year: 2010

Telmisartan shows antihypertensive and several pleiotropic effects that interact with metabolic pathways. In the present study we tested the hypothesis that telmisartan prevents adipogenesis in vitro and weight gain in vivo through activation of peroxisome proliferator-activated receptor (PPAR)-δ- dependent pathways in several tissues. In vitro, telmisartan significantly upregulated PPAR-δ expression in 3T3-L1 preadipocytes in a time-and dose-dependent manner. Other than enhancing PPAR-δ expression by 68.2±17.3% and PPAR-δ activity by 102.0±9.0%, telmisartan also upregulated PPAR-γ expression, whereas neither candesartan nor losartan affected PPAR-δ expression. In vivo, long-term administration of telmisartan significantly reduced visceral fat and prevented high-fat diet-induced obesity in wild-type mice and hypertensive rats but not in PPAR-δ knockout mice. Administration of telmisartan did not influence food intake in mice. Telmisartan influenced several lipolytic and energy uncoupling related proteins (UCPs) and enhanced phosphorylated protein kinase A and hormone sensitive lipase but reduced perilipin expression and finally inhibited adipogenesis in 3T3-L1 preadipocytes. Telmisartan-associated reduction of adipogenesis in preadipocytes was significantly blocked after PPAR-δ gene knockout. Chronic telmisartan treatment upregulated the expressions of protein kinase A, hormone-sensitive lipase, and uncoupling protein 1 but reduced perilipin expression in adipose tissue and increased uncoupling protein 2 and 3 expression in skeletal muscle in wild-type mice but not in PPAR-δ knockout mice. We conclude that telmisartan prevents adipogenesis and weight gain through activation of PPAR-δ-dependent lipolytic pathways and energy uncoupling in several tissues. © 2010 American Heart Association, Inc. Source


Gallwitz B.,University Hospital of Tuebingen | Hamann A.,Medizinische Klinik IV
Diabetes Aktuell | Year: 2013

Treatment of type 2 diabetes remains a challenge in spite of new treatment options and modern types of insulin, in particular for obese subjects. It is frequently difficult to achieve strict HbA1c targets, and even in case of success this frequently happens at the expense of weight gain and an increased risk of hypoglycemia. Therefore, new treatment strategies are needed in particular for the high risk patient population with obesity, insulin resistance and inadequately high HbA1c. From a pathophysiological perspective, it is reasonable to combine insulin and glucagon-like peptide 1 (GLP 1) receptor agonists, although hard clinical data regarding the reduction of micro- and macrovascular complications are still missing. This review summarizes the clinical data available and illustrates that combined treatment with insulin plus GLP-1 receptor agonist will frequently achieve improved glycemic control and results in weight loss, with only a slightly increased risk of hypoglycemia, but associated with the known gastrointestinal side effect profile of GLP-1 receptor agonists. Additionally, this review explains why short-acting GLP-1 receptor agonists that are associated with a marked decrease of postprandial blood glucose levels may be particularly suitable for a combination with basal insulin, whereas long-acting GLP-1 receptor agonists that primarily aim at fasting blood glucose control may be more suitable for a combination with more complex insulin regimens such as the intensified conventional insulin therapy, although comparative clinical data are also missing here. © Georg Thieme Verlag KG Stuttgart New York. Source


Gallwitz B.,Medizinische Klinik IV
Pediatric Nephrology | Year: 2010

Treatment options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In adult medicine, both treatment options are attractive and more commonly used because of their action and safety profile. The incretinbased therapies stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives an overview of the mechanism of action and the substances and clinical data available. © IPNA 2010. Source


With incretin based therapies (DPPIV inhibitors and GLP-1 analogues) novel antidiabetic drugs are available since 2007. In contrast to other insulinotropic compounds, they stimulate insulin secretion in a glucose-dependent manner during hyperglycemia and they do not have an intrinsic risk for causing hypoglycaemia. Additionally, they inhibit glucagon secretion and have a favourable effect on body weight. DPPIV inhibitors (sitagliptin, saxagliptin and vildagliptin) can be used for combination therapy with metformin, glitazones and sulfonylureas according to the guidelines. Their effectiveness is comparable to other oral antidiabetics. DPPIV inhibitors are weight neutral. Their tolerability is good, specific side effects are not known. GLP-1 analogues (exenatide and liraglutide) are injectable medications with similar indications according to the guidelines. They are more effective than DPPIV inhibitors and additionally allow weight loss. Further incretin based substances are in the approval process or in clinical development. © Schattauer 2010. Source


Gallwitz B.,Medizinische Klinik IV
Handbook of Experimental Pharmacology | Year: 2015

Novel therapeutic options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were introduced in 2005. Incretinbased therapies consist of two classes: (1) the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor and (2) dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) as oral medications raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In type 2 diabetes therapy, incretin-based therapies are attractive and more commonly used due to their action and safety profile. Stimulation of insulin secretion and inhibition of glucagon secretion by the above-mentioned agents occur in a glucose-dependent manner. Therefore, incretinbased therapies have no intrinsic risk for hypoglycemias. GLP-1 receptor agonists allow weight loss; DPP-4 inhibitors are weight neutral. This review gives an overview on the mechanism of action and the substances and clinical data available. © Springer-Verlag Berlin Heidelberg 2011. Source

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