Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.

The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.

[Orthotopic liver transplantation with no veno-venous bypass].

OBJECTIVE: To assess the feasibility and outcome of orthotopic liver transplantation (OLT) with no veno-venous bypass (VVB) in adult patients. METHODS: Between 1999 and June 2001, 43 adult patients were subjected to orthotopic liver transplantations with veno-venous bypass (28), or no veno-venous bypass (15). RESULTS: There was no significant difference in mean serum creatinine on day 3 and gas discharge time in patients with veno-venous bypass or not. With no veno-venous bypass, the average operative time was 5.6 +/- 1.4 h, median amount of blood loss during operation was 4 200 +/- 850 ml, median amount of blood transfused intraoperatively was 4 800 +/- 920 ml, and median intensive care unit stay was 6.3 days. All these were lower or shorter than those of the patients with veno-venous bypass. CONCLUSIONS: Orthotopic liver transplantation with no veno-venous bypass is safe and can be performed in the majority of adult patients. Liver transplantation with no veno-venous bypass is associated with shorter total operating time, lower blood product usage, and shorter intensive care unit stay compared with standard technique of OLT with routine use of VVB.

NO-1886 suppresses diet-induced insulin resistance and cholesterol accumulation through STAT5-dependent upregulation of IGF1 and CYP7A1.

Insulin resistance and dyslipidemia are both considered to be risk factors for metabolic syndrome. Low levels of IGF1 are associated with insulin resistance. Elevation of low-density lipoprotein cholesterol (LDL-C) concomitant with depression of high-density lipoprotein cholesterol (HDL-C) increase the risk of obesity and type 2 diabetes mellitus (T2DM). Liver secretes IGF1 and catabolizes cholesterol regulated by the rate-limiting enzyme of bile acid synthesis from cholesterol 7alpha-hydroxylase (CYP7A1). NO-1886, a chemically synthesized lipoprotein lipase activator, suppresses diet-induced insulin resistance with the improvement of HDL-C. The goal of the present study is to evaluate whether NO-1886 upregulates IGF1 and CYP7A1 to benefit glucose and cholesterol metabolism. By using human hepatoma cell lines (HepG2 cells) as an in vitro model, we found that NO-1886 promoted IGF1 secretion and CYP7A1 expression through the activation of signal transducer and activator of transcription 5 (STAT5). Pretreatment of cells with AG 490, the inhibitor of STAT pathway, completely abolished NO-1886-induced IGF1 secretion and CYP7A1 expression. Studies performed in Chinese Bama minipigs pointed out an augmentation of plasma IGF1 elicited by a single dose administration of NO-1886. Long-term supplementation with NO-1886 recovered hyperinsulinemia and low plasma levels of IGF1 suppressed LDL-C and facilitated reverse cholesterol transport by decreasing hepatic cholesterol accumulation through increasing CYP7A1 expression in high-fat/high-sucrose/high-cholesterol diet minipigs. These findings indicate that NO-1886 upregulates IGF1 secretion and CYP7A1 expression to improve insulin resistance and hepatic cholesterol accumulation, which may represent an alternative therapeutic avenue of NO-1886 for T2DM and metabolic syndrome.

NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats.

Evidences indicate that a complex relationship exists among sleep disorders, obesity and insulin resistance. NEU-P11 is a novel melatonin agonist used in treatment of psychophysiological insomnia, and in animal studies NEU-P11 showed sleep-promoting effect. In this study, we applied NEU-P11 on obese rats to assess its potential melatoninergic effects in vivo. Obese models were established using high-fat/high-sucrose-fed for 5 months. NEU-P11 (10mg/kg)/melatonin (4mg/kg)/vehicle were administered by a daily intraperitoneal injection respectively for 8 weeks. Our results showed that NEU-P11 or melatonin inhibited both body weight gain and deposit of abdominal fat with no influence on food intake. The impaired insulin sensitivity and antioxidative potency were improved and the levels of plasma glucose, total cholesterol (TC), triglycerides (TG) decreased with an increased in HDL-cholesterol (HDL-c) after NEU-P11 or melatonin administration. These data suggest that NEU-P11, like melatonin, decreased body weight gain and improved insulin sensitivity and metabolic profiles in obese rats. We conclude that NEU-P11 has a melatoninergic effect on regulating body weight in obese rats and also improving metabolic profiles and efficiently enhancing insulin sensitivity.

Adiponectin decreases plasma glucose and improves insulin sensitivity in diabetic Swine.

To investigate the effects of recombinant human adiponectin on the metabolism of diabetic swine induced by feeding a high-fat/high-sucrose diet (HFSD), diabetic animal models were constructed by feeding swine with HFSD for 6 months. The effects of recombinant adiponectin were assessed by detecting the change of plasma glucose levels by commercially available enzymatic method test kits and evaluating the insulin sensitivity by oral glucose tolerance test (OGTT). About 1.5 g purified recombinant adiponectin was produced using a 15-liter fermenter. A single injection of purified recombinant human adiponectin to diabetic swine led to a 2- to 3-fold elevation in circulating adiponectin, which triggered a transient decrease in basal glucose level (P<0.05). This effect on glucose was not associated with an increase in insulin level. Moreover, after adiponectin injection, swine also showed improved insulin sensitivity compared with the control (P<0.05). Adiponectin might have the potential to be a glucose-lowering agent for metabolic disease. Adiponectin as a potent insulin enhancer linking adipose tissue and glucose metabolism could be useful to treat insulin resistance.