Nicotinamide protects against skeletal muscle atrophy in streptozotocin-induced diabetic mice.

Context: Skeletal muscle atrophy is a complication of diabetes, partially induced by nicotinamide adenine dinucleotide (NAD+) deficiency. Objective: This study investigates the potential of nicotinamide (NAM) supplementation, a precursor of NAD+, against muscle atrophy. Methods: Mice were separated into normal control group, normal control with NAM administration group, diabetic group, and diabetic mice with NAM administration group. Basic characteristics, muscle weight, maximal grip strength, and myofibers cross-sectional area were analysed. Markers reflecting muscle atrophy and hypertrophy, and transforming growth factor ß1/Smad2 (TGF-ß1/Smad2) pathway were examined. Results: NAM did not influence body weight and blood glucose. In diabetic mice, NAM increased NAD+ level, rescued muscle weight and strength loss, and increased myofibers cross-sectional area. NAM inhibited MuRF1 and Atrogin1, while elevated phosphorylation of Akt. Overactivation of TGF-ß1/Smad2 pathway was repressed by NAM. Conclusion: NAM ameliorated diabetic muscle atrophy by rebalancing protein anabolism and catabolism, probably through de-activation of TGF-ß1/Smad2 signaling.

Myo-inositol lowers the risk of developing gestational diabetic mellitus in pregnancies: A systematic review and meta-analysis of randomized controlled trials with trial sequential analysis.

AIMS: to explore the potential benefit of myo-inositol on pregnant women with high risk of developing gestational diabetes mellitus (GDM). METHODS: Pubmed, Embase, and Cochrane library were systematically searched for randomized controlled trials (RCTs) comparing myo-inositol with placebo for pregnant women with risk factors of GDM. Primary outcome were the incidence of GDM and birth weight. Secondary outcomes included fasting, 1h, and 2h oral glucose tolerance test (OGTT), and complications. Trial sequential analysis (TSA) was performed on primary outcomes to confirm the pooled results. Number needed to treat (NNT) was calculated to show the efficacy of myo-inositol supplement. RESULTS: Four RCTs with 586 patients were included. Compared with placebo, patients with myo-inositol supplement had significantly lower the risk of developing GDM (RR=0.44, 95% CI [0.32, 0.62], P<0.0001) without heterogeneity (I2=0%, P=0.99), which was confirmed by TSA. NNT was 6.2 and rounded to 7. Myo-inositol did not significantly decrease birth weight (60.60g, 95% CI [-177.21, 56.02], P=0.31) with significant heterogeneity (I2=52%, P=0.12), but was not confirmed by TSA. Myo-inositol supplement was related to significantly lower fasting, 1h, and 2h OGTT value and the incidence of pre-term delivery. Difference was not significant between myo-inositol and placebo regarding incidence of other complications. CONCLUSION: Myo-inositol is related to lower incidence of GDM, as well as fasting, 1h, and 2h OGTT value, in pregnant women with high risk of this condition. Myo-inositol might not be related to a lower birth weight, which needs further confirmation.

Exogenous kallikrein protects against diabetic nephropathy.

The kallikrein-kinin system has been shown to be involved in the development of diabetic nephropathy, but specific mechanisms are not fully understood. Here, we determined the renal-protective role of exogenous pancreatic kallikrein in diabetic mice and studied potential mechanisms in db/db type 2 diabetic and streptozotocin-induced type 1 diabetic mice. After the onset of diabetes, mice were treated with either pancreatic kallikrein (db/db+kallikrein, streptozotocin+kallikrein) or saline (db/db+saline, streptozotocin+saline) for 16 weeks, while another group of streptozotocin-induced diabetic mice received the same treatment after onset of albuminuria (streptozotocin'+kallikrein, streptozotocin'+saline). Db/m littermates or wild type mice were used as non-diabetic controls. Pancreatic kallikrein had no effects on body weight, blood glucose and blood pressure, but significantly reduced albuminuria among all three groups. Pathological analysis showed that exogenous kallikrein decreased the thickness of the glomerular basement membrane, protected against the effacement of foot process, the loss of endothelial fenestrae, and prevented the loss of podocytes in diabetic mice. Renal fibrosis, inflammation and oxidative stress were reduced in kallikrein-treated mice compared to diabetic controls. The expression of kininogen1, tissue kallikrein, kinin B1 and B2 receptors were all increased in the kallikrein-treated compared to saline-treated mice. Thus, exogenous pancreatic kallikrein both prevented and ameliorated diabetic nephropathy, which may be mediated by activating the kallikrein-kinin system.