Most information used to evaluate diabetic statuses is collected at a special time-point, such as taking fasting plasma glucose test and providing a limited view of individual's health and disease risk. As a new parameter for continuously evaluating personal clinical statuses, the newly developed technique "continuous glucose monitoring" (CGM) can characterize glucose dynamics. By calculating the complexity of glucose time series index (CGI) with refined composite multi-scale entropy analysis of the CGM data, the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes (P for trend < 0.01). Furthermore, CGI was significantly associated with various parameters such as insulin sensitivity/secretion (all P < 0.01), and multiple linear stepwise regression showed that the disposition index, which reflects β-cell function after adjusting for insulin sensitivity, was the only independent factor correlated with CGI (P < 0.01). Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.
Humans ; Glucose ; Blood Glucose ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2/diagnosis* ; Blood Glucose Self-Monitoring ; Time Factors ; Insulin

Objective: To analyze the difference in blood uric acid levels between patients with polycystic ovary syndrome (PCOS) and healthy women of childbearing age, and to investigate the correlation between body composition and blood uric acid levels. Methods: A total of 153 eligible childbearing age patients with PCOS treated at Tianjin Medical University General Hospital from January 2018 to March 2022 were selected, and 153 healthy women with normal menstruation were selected as the control group. Fasting blood uric acid levels were measured by venous blood test, and body composition was measured by a body composition analyzer. Group comparisons were made to analyze the correlation between body composition and blood uric acid levels. Results: The incidence of hyperuricemia was higher in patients with PCOS than that in the control group [30.1% (46/153) vs 2.0% (3/153)], with a statistically significant difference (χ²=44.429, P<0.001). Blood uric acid level was also significantly higher in patients with PCOS than that in the control group [(371±98) vs (265±67) μmol/L; t=11.170, P<0.001]. Among PCOS patients, there were statistically significant differences in weight, body mass index (BMI), body fat mass, skeletal muscle mass, percent body fat, lean body weight, fat mass/lean body weight, percent skeletal muscle, and visceral fat level between the hyperuricemia group and the normal blood uric acid group (all P<0.001), but no significant difference was observed in waist-hip ratio (P=0.348). The following body composition indicators: weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, visceral fat level, lean body weight, and fat mass/lean body weight in all subjects, the PCOS patients and the control group, were positively correlated with blood uric acid levels (all P<0.01). The blood uric acid level in PCOS obese patients was higher than that in non-obese PCOS patients, and the difference was statistically significant [(425±83) vs (336±91) μmol/L; t=6.133, P<0.001]. The blood uric acid level in central obesity PCOS patients was also higher than that in non-central obesity PCOS patients [(385±95) vs (299±79) μmol/L], the difference was statistically significant (t=4.261, P<0.001). The blood uric acid level in normal-weight obese PCOS patients was higher than that in normal-weight non-obese PCOS patients [(333±73) vs (277±54) μmol/L], and the difference was statistically significant (t=2.848, P=0.006). Blood uric acid levels in normal-weight [(315±74) vs (255±67) μmol/L], overweight [(362±102) vs (276±57) μmol/L], and obese PCOS patients [(425±83) vs (303±74) μmol/L] were all higher than those in the corresponding control groups, with statistically significant differences (all P<0.001). Conclusions: PCOS patients have a higher incidence of hyperuricemia than healthy women of childbearing age. Blood uric acid levels are closely correlated with body composition indicators, such as weight, BMI, waist-hip ratio, body fat mass, skeletal muscle mass, percent body fat, and visceral fat level. Body composition analysis of women with PCOS could help identify potentially obese people more accurately and carry out individualized treatment, thereby reducing the risk of metabolic abnormalities.
Humans ; Female ; Polycystic Ovary Syndrome/complications* ; Uric Acid ; Hyperuricemia/complications* ; Insulin ; Body Composition/physiology* ; Obesity/complications* ; Body Mass Index

Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.
Humans ; Amino Acids, Branched-Chain/metabolism* ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2 ; Insulin/pharmacology* ; Keto Acids/metabolism*

To explore the effect and mechanism of Zuogui Pills in promoting neural tissue recovery and functional recovery in mice with ischemic stroke. Male C57BL/6J mice were randomly divided into a sham group, a model group, and low-, medium, and high-dose Zuogui Pills groups(3.5, 7, and 14 g·kg~(-1)), with 15 mice in each group. The ischemic stroke model was established using photochemical embolization. Stiker remove and irregular ladder walking behavioral tests were conducted before modeling and on days 7, 14, 21, and 28 after medication. Triphenyl tetrazolium chloride(TTC) staining was performed on day 3 after modeling, and T2-weighted imaging(T2WI) and diffusion-weighted imaging(DWI) were performed on day 28 after medication to evaluate the extent of brain injury. Hematoxylin-eosin(HE) staining was performed to observe the histology of the cerebral cortex. Axonal marker proteins myelin basic protein(MBP), growth-associated protein 43(GAP43), mammalian target of rapamycin(mTOR), and its downstream phosphorylated s6 ribosomal protein(p-S6), as well as mechanism-related proteins osteopontin(OPN) and insulin-like growth factor 1(IGF-1), were detected using immunofluorescence and Western blot. Zuogui Pills had a certain restorative effect on the neural function impairment caused by ischemic stroke in mice. TTC staining showed white infarct foci in the sensory-motor cortex area, and T2WI imaging revealed cystic necrosis in the sensory-motor cortex area. The Zuogui Pills groups showed less brain tissue damage, fewer scars, and more capillaries. The number of neuronal axons in those groups was higher than that in the model group, and neuronal activity was stronger. The expression of GAP43, OPN, IGF-1, and mTOR proteins in the Zuogui Pills groups was higher than that in the model group. In summary, Zuogui Pills can promote the recovery of neural function and axonal growth in mice with ischemic stroke, and its mechanism may be related to the activation of the OPN/IGF-1/mTOR signaling pathway.
Mice ; Animals ; Male ; Ischemic Stroke ; Recovery of Function/physiology* ; Insulin-Like Growth Factor I/pharmacology* ; Mice, Inbred C57BL ; TOR Serine-Threonine Kinases/metabolism* ; Stroke/drug therapy* ; Brain Ischemia/drug therapy* ; Mammals/metabolism*

The renin angiotensin system (RAS) appears to influence male fertility at multiple levels. In this work, we analyzed the relationship between the RAS and DNA integrity. Fifty male volunteers were divided into two groups (25 each): control (DNA fragmentation ≤20%) and pathological (DNA fragmentation >20%) cases. Activities of five peptidases controlling RAS were measured fluorometrically: prolyl endopeptidase (which converts angiotensin [A] I and A II to A 1-7), neutral endopeptidase (NEP/CD10: A I to A 1-7), aminopeptidase N (APN/CD13: A III to A IV), aminopeptidase A (A II to A III) and aminopeptidase B (A III to A IV). Angiotensin-converting enzyme (A I to A II), APN/CD13 and NEP/CD10 were also assessed by semiquantitative cytometry and quantitative flow cytometry assays, as were the receptors of all RAS components: A II receptor type 1 (AT1R), A II receptor type 2 (AT2R), A IV receptor (AT4R or insulin-regulated aminopeptidase [IRAP]), (pro)renin receptor (PRR) and A 1-7 receptor or Mas receptor (MasR) None of the enzymes that regulate levels of RAS components, except for APN/CD13 (decrease in fragmented cells), showed significant differences between both groups. Micrographs of RAS receptors revealed no significant differences in immunolabeling patterns between normozoospermic and fragmented cells. Labeling of AT1R (94.3% normozoospermic vs 84.1% fragmented), AT4R (96.2% vs 95.3%) and MasR (97.4% vs 87.2%) was similar between the groups. AT2R (87.4% normozoospermic vs 63.1% fragmented) and PRR (96.4% vs 48.2%) were higher in non-fragmented spermatozoa. These findings suggest that fragmented DNA spermatozoa have a lower capacity to respond to bioactive RAS peptides.
Angiotensins ; DNA Fragmentation ; Humans ; Insulin ; Male ; Renin-Angiotensin System/physiology* ; Spermatozoa

Simiao Wan (SMW) is a traditional Chinese formula, including Atractylodis Rhizoma, Achyranthis Bidentatae Radix, Phellodendri Chinensis Cortex and Coicis Semen at the ratio of 1:1:2:2. It can be used to the treatment of diabetes. However, its bioactive compounds and underlying mechanism are unclear. This study aimed to screen the antilipolytic fraction from SMW and investigate its therapeutic mechanisms on hepatic insulin resistance. Different fractions of SMW were prepared by membrane separation combined with macroporous resin and their antilipolytic activities were screened in fasted mice. The effects of 60% ethanol elution (ESMW) on lipolysis were investigated in 3T3-L1 adipocytes stimulated by palmitic acid (PA) and high fat diet (HFD)-fed mice. In our study, ESMW is the bioactive fraction responsible for the antilipolytic activity of SMW and 13 compounds were characterized from ESMW by UHPLC-QTOF-MS/MS. ESMW suppressed protein kinase A (PKA)-hormone-sensitive lipase (HSL) related lipolysis and increased AMP-activated protein kinase (AMPK) phosphorylation in PA challenged 3T3-L1 adipocytes. AMPKα knockdown abolished the inhibitory effects of ESMW on IL-6 and HSL pSer-660, revealing that the antilipolytic and anti-inflammatory activities of ESMW are AMPK dependent. Furthermore, ESMW ameliorated insulin resistance and suppressed lipolysis in HFD-fed mice. It inhibited diacylglycerol accumulation in the liver and inhibited hepatic gluconeogenesis. Conditional medium collected from ESMW-treated 3T3-L1 cells ameliorated insulin action on hepatic gluconeogenesis in liver cells, demonstrating the antilipolytic activity contributed to ESMW beneficial effects on hepatic glucose production. In conclusion, ESMW, as the antilipolytic fraction of SMW, inhibited PKA-HSL related lipolysis by activating AMPK, thus inhibiting diacylglycerol (DAG) accumulation in the liver and thereby improving insulin resistance and hepatic gluconeogenesis.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Insulin/metabolism* ; Lipolysis/physiology* ; Liver/metabolism* ; Mice ; Tandem Mass Spectrometry

Skeletal muscle is the largest organ of human body, which completes 80%-90% of glucose intake stimulated by insulin, and is closely related to the occurrence and development of insulin resistance (IR). Skeletal muscle is one of the main places of lipid metabolism, and lipid metabolites participate in skeletal muscle metabolism as signal molecules. Fatty acids regulate skeletal muscle insulin sensitivity through insulin signaling pathway, inflammatory response and mitochondrial function. Saturated fatty acids (SFAs) induce insulin resistance by impairing insulin signal transduction, inducing mitochondrial dysfunction and inflammatory response, while unsaturated fatty acids reverse the adverse effects of SFAs and ameliorate IR by enhancing insulin signal transduction and anti-inflammatory effect. In addition, disorders of lipid metabolism in skeletal muscle cause accumulation of harmful metabolic intermediates, such as diacylglycerol, ceramide and long-chain acyl-coenzyme A, and induce IR by directly or indirectly damaging insulin signaling pathway. This article reviews the research progress of lipid metabolic intermediates regulating insulin sensitivity in skeletal muscle, which will help to better understand the pathogenesis of diabetes.
Humans ; Insulin Resistance/physiology* ; Muscle, Skeletal/metabolism* ; Insulin/metabolism* ; Lipid Metabolism ; Fatty Acids/metabolism*

OBJECTIVE: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD. METHODS: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pSGSK3α, and the number of hippocampal senile plaques (SP) was observed. RESULTS: The proteins of P85α, P110α, GSK3α and pSGSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group (<0.001), and the distribution level of pSGSK3α, P85α and P110α was significantly decreased (<0.01, <0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased (<0.001), and the distribution level of pSGSK3α, P85α and P110α in hippocampus was significantly increased (<0.05, <0.001). The Western blot results showed compared with the control group, the expression of pSGSK3α, P85α and P110α as well as the ratio of pSGSK3α/GSK3α in the hippocampus in the model group were significantly decreased (<0.001), and the expression of GSK3α was increased (<0.05); compared with the model group, the expression of pSGSK3α, P85α, P110α and the ratio of pSGSK3α/GSK3α in the hippocampus in the treatment group were significantly increased (<0.01, <0.001), and the expression of GSK3α was decreased (<0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased (<0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased (<0.01). CONCLUSION EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.
Alzheimer Disease ; therapy ; Animals ; Electroacupuncture ; Hippocampus ; physiology ; Insulin ; physiology ; Male ; Mice ; Mice, Transgenic ; Random Allocation ; Signal Transduction

Insulin resistance is a common pathophysiological mechanism of obesity and type 2 diabetes mellitus. Skeletal muscle is one of the major target organs of insulin-mediated glucose uptake, metabolism and utilization, and it is the earliest and most important site of insulin resistance. Studies have shown that the impairments of glucose uptake, insulin signaling pathway and mitochondrial biosynthesis are closely related to skeletal muscle insulin resistance. When insulin resistance develops in skeletal muscle, multiple microRNAs (miRNAs) are up-regulated (miR-106b, miR-23a, miR-761, miR-135a, Let-7 and miR-29a) or down-regulated (miR-133a, miR-149 and miR-1). They participate in the regulation of skeletal muscle glucose uptake, insulin signaling pathway and mitochondrial biogenesis, and thus play important roles in the occurrence and development of skeletal muscle insulin resistance. Therefore, these miRNAs may serve as potential targets for the treatment of skeletal muscle insulin resistance or diabetes.
Diabetes Mellitus, Type 2 ; Humans ; Insulin ; Insulin Resistance ; MicroRNAs ; genetics ; Muscle, Skeletal ; physiology

More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.
Animals ; Diabetes Mellitus, Experimental ; physiopathology ; Down-Regulation ; Insulin ; Insulin Receptor Substrate Proteins ; physiology ; Insulin Resistance ; MicroRNAs ; genetics ; Myocytes, Cardiac ; physiology ; Rats