| Objective: Diabetes is mainly divided into type I and type II.Type II diabetes(T2D)is the most common type,accounting for more than 90% of diabetes.Its main features are insulin resistance and persistent hyperglycemia caused by pancreatic ?-cell dysfunction.Sedentary,high-fat,high-sugar diet,plus more intake of refined sugar or monosaccharide,can maintain the body's hyperglycemia for a long time.At present,the treatment of diabetes mainly uses conventional hypoglycemic drugs,while reducing the intake of high-calorie and high-sugar foods,and the combination of drugs that inhibit postprandial blood glucose.In order to better control blood sugar and improve the quality of life of diabetic patients,scholars are looking for a sugar alcohol that has a lower caloric value,lower glycemic index,and lowers postprandial blood glucose compared with sucrose.Muscle inositol,one of the inositol isomers,is similar in structure to glucose and is found in almost all foods.Muscle inositol is involved in glucose transporter activation and glucose utilization,and also improves glucose metabolism,relieves insulin resistance,and lowers blood lipids in postmenopausal metabolic syndrome patients.It has been reported in the literature that supplementation with muscle inositol regulates glycolipid metabolism,which is closely related to the pathogenesis of T2 D.However,it has not yet been fully established that muscle inositol affects the uptake of glucose by muscles or intestines and its mechanism.Therefore,this study intends to investigate the effects of muscle inositol on the absorption of glucose in muscle and intestine of normal and diabetic rats by constructing a rat model of type II diabetes by in vitro and in vivo experiments,elucidating muscle inositol hypoglycemia and promoting glucose metabolism.Through the application of muscle inositol adjuvant therapy in patients with type II diabetes,to explore the effect and mechanism of muscle inositol on glucose metabolism in diabetic patients.Methods: Diabetic model preparation: The rats were fasting for 12 hours before the establishment of the model.The rats were intraperitoneally injected with 35 mg/kg 1% streptozotocin(STZ)solution.After one week feeding,the same dose of streptozotocin(STZ)solution was intraperitoneally injected on the 8th day.The fasting blood glucose of rats was measured by blood from tail tip.The rats with fasting blood glucose(> 7.8 mmol/L)and postprandial blood glucose(> 11.1 mmol/L)were selected as diabetic models for follow-up study.In vitro studies: 1.Glucose absorption and uptake experiments Rats were fasted overnight,abdominal anesthesia,and the rat jejunum and gastrocnemius muscle were cut open for glucose absorption and uptake experiments.The rat jejunum and gastrocnemius muscle were placed in Kerb's(Kb)solution containing different concentrations of myo-inositol,and the glucose concentration in Kb solution was measured before the experiment and after 1-2 h.2.Effects of muscle inositol on the tension of gastrointestinal smooth muscle strips in normal and diabetic rats The rats were divided into 6 groups:(1)normal rats with NS group;(2)normal rats with myo-inositol group;(3)normal rats with acarbose group;(4)diabetic rats with NS group;(5)diabetic rats with myo-inositol group;(5)diabetic rats with acarbose group.The gastrointestinal tract of rats was isolated after overnight fasting and abdominal anesthesia to observe the effect of inositol on the muscle tension of gastric circular smooth muscle and intestinal smooth muscle in normal and diabetic rats.NS,muscle inositol and acarbose were added to the perfusion tank to achieve a final concentration of NS,muscle inositol and acarbose in the perfusate muscle tank of 9 g/L,1 g/L and 100 mg/,respectively.L,incubate for 30 minutes,then add 10?mol/L CCh,record the basal tension(g)of the curve of gastric and intestinal smooth muscles after contraction,and calculate the effect of muscle inositol and acarbose on the contraction of CCh.In vivo research: 1.Effects of intragastrical administration myo-inositol on blood glucose and intestinal glucose uptake index in normal and diabetic rats A rat model of type II diabetes was prepared,the normal drinking water of the rats was changed into a 10% fructose solution,and 30 mg/kg of streptozotocin was intraperitoneally administered daily for one week,then the postprandial blood glucose of the rats was measured.Rats with postprandial blood glucose >300 mg/dl as follow-up study in II diabetic rats.The rats were divided into 6 groups:(1)normal rats with glucose control group;(2)normal rats with myo-inositol group;(3);normal rats with acarbose group;(4)diabetic rats with glucose control group;(5)diabetic rats with myo-inositol group;(6)diabetic rats with acarbose group The rats were anesthetized by inhalation of sevoflurane for 1 hour.Blood draw and glucose oxidase-peroxidase method was used to detect the content of glucose in plasma.The stomach,duodenum,jejunum,ileum,cecum and colon were separated.After weighing the tissues,the contents of each intestine were weighed,the glucose concentration was measured,and the glucose absorption rate in the intestinal segment was calculated.2.Effects of intramuscular inositol on gastric emptying rate and intestinal propulsion rate in normal and diabetic rats The rats were divided into 6 groups:(1)normal rats with NS group;(2)normal rats with myo-inositol group;(3)normal rats with acarbose group;(4)diabetic rats with NSgroup;(5)diabetic rats with myo-inositol group;(6)diabetic rats with acarbose group.All the gastric lavage fluid contained 0.05% phenol red.The rats were anesthetized by inhalation of sevoflurane for 1 hour.The gastric,duodenum,jejunum,ileum,cecum and colon were separated.The contents of each gastrointestinal segment were weighed and the concentration of phenol red was detected.The gastric emptying and the small intestinal propulsion rate were calculated.Clinical research: 200 patients with type 2 diabetes who were admitted to the Affiliated Hospital of Qingdao University from October 2016 to October 2017 were randomly divided into the drug group and the control group(n=100).All patients were continuously monitored for blood glucose and body mass index after admission,and patients were treated with a combination of life therapy and drug therapy.In the experimental group,in addition to conventional drug treatment,2 g of muscle inositol was orally administered half an hour before breakfast,and 2 g of dextrin was orally administered to the control group.Biochemical methods were used to detect fasting blood glucose(FBG),postprandial 2 h blood glucose(2 h PG),glycosylated hemoglobin(Hb AIC)in diabetic patients,and plasma adiponectin and tumor necrosis factor-?(TNF-?)were detected by ELISA.Interleukin-6(IL-6)content.Results: 1.In vitro studies showed that with the increase of myo-inositol concentration,the absorption of glucose in the jejunum of normal rats was significantly reduced in a dosedependent manner(P <0.05-0.001),and the maximum effective dose of myo-inositol was 40 mmol/L..2.With the increase of myo-inositol concentration,the glucose uptake of the gastrocnemius muscle of normal rats increased significantly,and showed a dose-dependent relationship(P <0.05~0.001);if the gastrocnemius muscle was in the insulin environment.The effect of myo-inositol on muscle glucose uptake was significantly increased(P <0.05-0.001).3.In vivo studies found that compared with normal rats,glucose intragastrical administration can significantly increase the blood glucose of diabetic rats at 1 h after meal(P <0.05).Myo-inositol or acarbose intragastrical administration was no significant change in blood glucose at 1 h after meal in normal rats(P >0.05),but it could significantly reduce blood glucose at 1 h after meal in diabetic rats(P <0.05).There was no significant difference in blood glucose lowering effect between myo-inositol with acarbose(P >0.05).4.Muscle inositol or acarbose gavage could significantly reduce the glucose absorption index of duodenum and jejunum in normal rats(P < 0.05);but in diabetic rats,muscle inositol gavage could significantly reduce the glucose absorption index of large jejunum and cecum(P < 0.05);Acarbose gavage significantly reduced the jejunal and colonic glucose absorption index in diabetic rats(P < 0.05).Compared with normal rats,the effect of muscle inositol or acarbose on reducing jejunal glucose absorption index in diabetic rats was significantly increased(P < 0.05).5.The gastric emptying rate of diabetic rats was significantly decreased by intragastrical administration myo-inositol or acarbose(P <0.05),but had no significant effect on normal rats(P >0.05).6.After incubation with muscle inositol or acarbose,the muscle contraction of CChinduced diabetic rats decreased(P <0.05),but had no significant effect on the contraction of gastric muscle strips in CCh-promoted rats(P>0.05).7.The duodenum,jejunum,cecum and colonic propulsion rate were significantly lower in diabetic rats than in normal rats(P <0.05).Intramuscular administration of myo-inositol significantly promoted intestinal propulsion in the jejunum,ileum,cecum,and colon in normal or diabetic rats(P <0.05);acarbose can only promote the duodenum,cecum and colon propulsion rate of diabetic rats(P <0.05).8.Incubation with muscle inositol significantly enhanced CZ-induced contraction of jejunum and ileum muscle strips in normal and diabetic rats(P < 0.05).Compared with normal rats,the ileal muscle strip contraction effect was significantly attenuated in CChinduced diabetic rats(P < 0.05).9.Clinical studies have shown that diabetic patients with myo-inositol(drug group)adjuvant treatment,the total effective rate of treatment with fasting blood glucose as a target is significantly increased(P <0.05);control group and drug group patients after treatment fasting blood glucose is significantly lower than before treatment(P <0.05),the decrease of fasting blood glucose in the drug group was significantly greater than that in the control group(P <0.05).10.In the drug group of myo-inositol adjuvant therapy,the total effective rate of 2 h after meal blood glucose treatment was significantly increased(P <0.05).The blood glucose of patients in the control group and the drug group was significantly lower than that before treatment(P < 0.05),and the decrease of 2 h after meal blood glucose in the drug group was significantly greater than that in the control group(P <0.05).11.In the control group and the drug group with myo-inositol,the levels of glycated hemoglobin(P <0.05),plasma inflammatory factors TNF-?(P <0.05)and IL-6(P <0.05)were significantly lower than those before treatment.Plasma adiponectin was significantly higher than before treatment(P <0.05);and in the drug group supplemented with myoinositol adjuvant therapy,these indicators were reduced(glycated hemoglobin,plasma inflammatory factors TNF-? and IL-6)or escalated(adiponectin)was significantly greater than that of the control group without myo-inositol(P <0.05).Conclusion: 1.Myo-inositol has hypoglycemic effect and can selectively participate in postprandial blood glucose regulation in diabetic rats;myo-inositol can reduce glucose absorption time by inhibiting glucose absorption in rat small intestine,thereby shortening glucose absorption time and promotes the uptake of glucose by gastrocnemius muscle and liver,then lowering blood glucose.The effect of myo-inositol on the hypoglycemic absorption of the jejunum of diabetic rats was significantly stronger than that in normal rats,which provided a good experimental basis for the treatment of muscle inositol clinical diabetes.2.In clinical myo-inositol combination therapy can reduce fasting blood glucose,postprandial 2 h blood glucose and glycosylated hemoglobin levels,increase blood adiponectin,and reduce plasma inflammatory factor expression.It is suggested that myoinositol can be used as one of the adjuvant treatments for hypoglycemia in patients with clinical diabetes.Combined with other studies,it is speculated that the hypoglycemic effect of muscle inositol may be related to the protective effect of ? islet cells. |
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