Gut microbiota-derived metabolites are novel targets for improving insulin resistance

The gut microbiota plays a key role in metabolic diseases. Gut-microbiota-derived metabolites are found in different dietary sources, including: Carbohydrate (acetate, propionate, butyrate, also known as short-chain fatty acids, as well as succinate); protein (hydrogen sulfide, indole, and phenylacetic acid); and lipids (resveratrol-, ferulic acid-, linoleic acid-, catechin- and berry-derived metabolites). Insulin resistance, which is a global pandemic metabolic disease that progresses to type 2 diabetes mellitus, can be directly targeted by these metabolites. Gut-microbiota-derived metabolites have broad effects locally and in distinct organs, in particular skeletal muscle, adipose tissue, and liver. These metabolites can modulate glucose metabolism, including the increase in glucose uptake and lipid oxidation in skeletal muscle, and decrease in lipogenesis and gluconeogenesis associated with lipid oxidation in the liver through activation of phosphatidylinositol 3-kinase - serine/threonine-protein kinase B and AMP-activated protein kinase. In adipose tissue, gut-microbiota-derived metabolites stimulate adipogenesis and thermogenesis, inhibit lipolysis, and attenuate inflammation. Importantly, an increase in energy expenditure and fat oxidation occurs in the whole body. Therefore, the therapeutic potential of current pharmacological and non-pharmacological approaches used to treat diabetes mellitus can be tested to target specific metabolites derived from intestinal bacteria, which may ultimately ameliorate the hyperglycemic burden.     

CCNG2 and CDK4 is associated with insulin resistance in adipose tissue

BackgroundThe involvement of cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4), cell cycle regulatory proteins, in adipose tissue metabolism and insulin resistance is still unknown. The objective of this study was to analyze CCNG2 and CDK4 levels in visceral (VAT) and subcutaneous adipose tissue (SAT) from nonobese and morbidly obese patients and their relationship with insulin resistance.MethodsWe studied the mRNA and protein levels of CCNG2 and CDK4 in VAT and SAT from 12 nonobese and 23 morbidly obese patients (11 with low [MO-L-IR] and 12 with high insulin resistance [MO-H-IR]).ResultsThe nonobese patients had a significantly greater CCNG2 expression in VAT (P = .004) and SAT (P<.001) than the MO-L-IR and MO-H-IR patients. The MO-H-IR patients had a significantly lower CDK4 expression in VAT than the MO-L-IR (P = .026), but similar to the nonobese patients. CDK4 and CCNG2 expression correlated significantly in VAT (r = 0.511, P<.001) and SAT (r = .535, P = .001). In different multiple regression analysis models, CCNG2 and CDK4 expression in VAT was mainly predicted by glucose (P = .047 and P = .008, respectively), and CCNG2 expression in SAT was mainly predicted by body mass index (P = .041). No significant associations were found with CDK4 expression in SAT. Moreover, VAT CCNG2 expression was the main determinant of the improvement in the homeostasis model assessment of insulin resistance index at 3 months after bariatric surgery (B = -271.7, P = .026).ConclusionOur data show for the first time that the human CCNG2 and CDK4 expression of VAT are inversely associated with glucose and insulin resistance.     

Loss of skeletal muscle mass is not specific to type 2 diabetes

Skeletal muscle is a massive insulin-sensitive tissue in the body. Loss of muscle mass is associated with mitochondrial dysfunction, and is often a result of diabetes. Insulin deficiency or insulin resistance can only be seen as reduced skeletal muscle mass. Diabetes is caused by insulin deficiency or insulin resistance; however, insulin resistance is not unique to diabetics. Insulin resistance also exists in many diseases.     

Amelioration of hypertension and insulin resistance by 1,25-dihydroxycholecalciferol in hemodialysis patients

The effects of i.v. 1,25-dihydroxycholecalciferol (DHCC) on blood pressure and insulin sensitivity were studied in 7 patients on maintenance hemodialysis and compared with 7 healthy controls. Three days after discontinuing oral 1,25-DHCC, the dialysis patients were evaluated by glucose clamp studies to quantitate insulin sensitivity, with (+D) and without (–D) a prior single dose of i.v. 1,25-DHCC at 2g/m². Blood pressure was measured just before the glucose studies. During –D studies, the patients were hypertensive (mean arterial blood pressure 108±2 mmHg, controls 84±4 mmHg,P<0.02) and insulin resistant (insulin sensitivity index 7.5±0.4 mg/kg·min per U per ml, controls 14.2±0.7,P<0.01) i.v. 1,25-DHCC significantly reduced the mean arterial blood pressure (96±3 mmHg,P<0.05) and increased insulin sensivity (10.9±0.5 mg/kg·min per U per ml,P<0.02) in the dialysis patients. I. V. 1,25-DHCC did not change blood pressure and insulin sensitivity in the control subjects. During –D studies, serum concentrations of 1,25-DHCC were significantly lower in patients than controls (P<0.02). Serum 1,25-DHCC during the +D studies increased to supraphysiological levels in both patients and controls. Serum concentrations of intact parathyroid hormone, total and ionized calcium, magnesium, potassium, urea nitrogen and creatinine were not different between the +D and –D studies in either the dialysis patients or the controls. These results suggest that pharmacological doses of 1,25-DHCC may have therapeutic value in the treatment of hypertension and insulin resistance in dialysis patients.     

免疫微生态肠内营养对腹腔感染患者术后胰岛素抵抗和感染并发症的影响

目的 探讨由益生菌、谷氨酰氨、深海鱼油和能全力组成的免疫微生态肠内营养对腹腔感染患者术后免疫状态和胰岛素抵抗以及感染并发症发生率的影响.方法 前瞻性纳入2010年9月至2013年4月山东省聊城市人民医院普通外科收治的96例上消化道穿孔患者,按信封法分为治疗组（48例,免疫微生态肠内营养）和对照组（48例,普通肠内营养）.分别于术前、术后第3和第7天检测两组患者空腹血糖、空腹胰岛素、对数化胰岛素抵抗指数（lnHOMA-IR）、降钙素原、T细胞亚群水平（CD3＋、CD4＋、CD8＋、CD4＋/CD8＋）及自然杀伤（NK）细胞计数并进行比较,观察对比两组患者术后感染并发症发生情况.结果 术前和术后第3天,两组患者免疫指标及胰岛素抵抗相关指标的比较,差异均无统计学意义（均P＞0.05）.术后第7天,治疗组CD4＋、CD4＋/CD8＋和NK细胞水平均明显高于对照组[（39.1±4.3）％比（30.1±5.7）％,P=0.043;1.76±0.21比1.36±0.12,P=0.038;（19.3±4.8）％比（13.3±3.2）％,P＝0.032];而空腹胰岛素、lnHOMA-IR及降钙素原水平明显低于对照组[（7.3±1.7） mU/L比（10.2±2.1） mU/L,P=0.041;0.60±0.05比0.88±0.06,P=0.039;（0.12±0.07） μg/L比（0.35±0.12）μg/L,P=0.028].治疗组术后感染并发症发生率[18.8％（9/48）]明显低于对照组[39.6％（19/48）,P=0.025].结论 对于由上消化道穿孔所致的腹腔感染患者,应用由益生菌、谷氨酰氨、深海鱼油及能全力组成的免疫微生态肠内营养,能改善免疫状态,降低术后胰岛素抵抗,减少术后感染并发症发生率.     

一种新的胰岛素抵抗的多囊卵巢综合征大鼠模型的建立

目的皮下注射脱氢表雄酮（DHEA）联合高脂高卡饮食喂养,建立一种新的胰岛素抵抗（IR）的多囊卵巢综合征（PCOS）大鼠模型。方法建立60只IR的PCOS雌鼠为造模组,13只同龄雌鼠为对照组。HE染色观察卵巢形态学变化,葡萄糖氧化酶法测定空腹血糖（FBG）,ELISA检测胰岛素样生长因子（IGF）-I、胰岛素样生长因子结合蛋白（IGFBPs）,放射免疫法测定血清空腹胰岛素（Fins）、睾酮（T）、雌二醇（E2）、卵泡刺激素（FSH）、黄体生成素（LH）,计算胰岛素敏感指数（ISI）和LH／FSH。结果与对照组比较,造模组大鼠卵巢呈多囊样改变,平均排卵数及排卵率、IGF-1、IGFBP-3、ISI、FSH明显降低（P〈0．05或P〈0．01）,FBG、Fins和IGFBP-1、T、E2、LH浓度以及LH／FSH显著升高（P〈0．05或P〈0．01）。结论皮下注射DHEA联合高脂高卡饮食,可成功诱导IR的PCOS大鼠模型。     

Type 2 diabetes mellitus: From a metabolic disorder to an inflammatory condition

Diabetes mellitus is increasing at an alarming rate and has become a global challenge.Insulin resistance intarget tissues and a relative deficiency of insulin secretion from pancreatic β-cells are the major features of type 2 diabetes(T2D).Chronic low-grade inflammation in T2 D has given an impetus to the field of immuno-metabolism linking inflammation to insulin resistance and β-cell dysfunction.Many factors advocate a causal link between metabolic stress and inflammation.Numerous cellular factors trigger inflammatory signalling cascades,and as a result T2 D is at the moment considered an inflammatory disorder triggered by disordered metabolism.Cellular mechanisms like activation of Tolllike receptors,Endoplasmic Reticulum stress,and inflammasome activation are related to the nutrient excess linking pathogenesis and progression of T2 D with inflammation.This paper aims to systematically review the metabolic profile and role of various inflammatory pathways in T2 D by capturing relevant evidence from various sources.The perspectives include suggestions for the development of therapies involving the shift from metabolic stress to homeostasis that would favour insulin sensitivity and survival of pancreatic β-cells in T2 D.     

不同麻醉和镇痛方法对胸科手术胰岛素抵抗及相关因素影响的研究

目的 研究不同麻醉和术后镇痛方式对胸科手术后胰岛素抵抗(insulin resistance,IR)的影响及相关因素.方法 60例胸科手术患者按随机数字表法随机分为两组:对照组(GA组,n=30),实验组(GEA组,n=30).GA组行全麻+术后静脉镇痛;GEA组行硬膜外麻醉复合全麻+术后硬膜外镇痛.分别于麻醉前、术毕...