Endocrine Abstracts

We previously have reported that short-term treatment of mice with recombinant hGH leads to significant increases in bodyweight (BW), lean body mass (LBM) and liver weight, but – unlike in humans – does not robustly increase circulating levels of IGF1. We now tested the hypothesis that formation of neutralizing antibodies in mice treated with rhGH could explain the lack of IGF1 response. Therefore, we intentionally induced antibody formation against hGH in female FVB...

Low-carbohydrate/high fat diets (LC-HFD) effectively induce body weight loss in both animals and humans; however, in rats this is paralleled by increased visceral adiposity contributing to impaired glucose tolerance. Estrogen inhibits adipose tissue accumulation, with estrogen deficient female animals displaying increased body weight and visceral adiposity with reduced insulin sensitivity, which can be reversed with estrogen replacement. Consistent with the effects seen in fem...

Moderate, ‘Atkin’s-style’ low-carbohydrate/high fat diets (LC-HFD) are claimed to induce weight loss in overweight subjects and to ameliorate glucose metabolism, whereas extreme ketogenic LC-HFD are used to treat neurological disorders like pediatric epilepsy. To investigate the effects of both types of LC-HFD on glucose and insulin metabolism independent of the energetic intake, we pair-fed male Wistar rats isoenergetic of standard rodent chow (CH) or one of tw...

High-fat/low carbohydrate (HF–LC) diets in humans, such as the Atkin’s diet, are claimed to work in an ad libitum setting. In a previous study, we had demonstrated reduced bodyweight (BW) gain in rats when pair-fed isocaloric amounts of a HF–LC compared to normal chow (CH). However, rats on HF–LC also showed increased body fat and low serum IGF-I. We now compared BW development, food intake and resting energy expenditure (EE) in an ad libitum setting in mal...

Impaired glucose tolerance and insulin sensitivity are established hallmarks of diabetes and it was speculated that also fructose tolerance could be impaired. However, investigation of fructose tolerance has been hampered by the lack of easy accessible pharmacodynamic markers. In humans, the hormone FGF21 has recently been demonstrated to be a sensitive pharmacodynamic marker responding to an oral fructose bolus and exhibiting a divergent secretion pattern in obese diabetic an...

Background: The development of recombinant biologics has had a major impact on many diseases. However, most biologics are rapidly cleared from the body and therefore require frequent injection regimens. There is therefore a need for technologies that allow the half-lives of these molecules to be extended in a predictable manner.HypothesisIncreasing numbers of N-linked glycosylation motifs between two GH molecules leads to gradually...

Objective: The exopeptidase dipeptidyl peptidase 4 (Dpp4) selectively cleaves N-terminal dipeptides from several substrates, including cytokines, growth factors, neuropeptides, and the incretin hormones. The systemic inhibition of Dpp4 by the so-called gliptins (oral Dpp4 inhibitors) represents an effective and established treatment option for type 2 diabetes (T2D). In the current study we investigated in healthy as well as in obese and diabetic mice if a liver selective knock...

Excess consumption of saturated fatty acids may lead to an increased production of ceramides that contribute to development of insulin resistance and type 2 diabetes. Substantial research demonstrated that inhibition of ceramide biosynthesis ameliorates atherosclerosis, hepatic steatosis, insulin resistance and obesity. However, as ceramides and their sphingolipid products are involved in multiple fundamental cellular processes, concerns exist about possible risks or adverse e...

Class 2a HDACs (i.e. HDAC 4, 5, 7 and 9) are involved in the regulation of gluconeogenesis and accordingly, their inhibition has been shown to result in lower blood glucose and improved pyruvate tolerance in diabetic mice. However, pan-inhibition of HDACs is not a viable approach for chronic treatment of type 2 diabetes (T2D) due to induction of severe side effects in various tissues. We now have investigated in vitro and in vivo efficacy and safety of a live...

Ketogenic low-carbohydrate/high fat diets (LC-HFD) induce weight loss in both animals and humans. However, a number of unwanted side effects with these diets have been reported. We have previously shown in male rats that LC-HFDs negatively affect bone growth and bone mineral density, possibly due to macronutrient-induced impairments of the GH/IGF-system. Given the importance of dietary macronutrients in the regulation of bone density in male rats, in this study we investigated...