This study aimed to examine the effect and underlying mechanism of Puerariae Lobatae Radix on insulin resistance in db/db mice with type 2 diabetes mellitus(T2DM) based on the analysis of intestinal flora. Fifty db/db mice were randomly divided into a model group(M group), a metformin group(YX group), a high-dose Puerariae Lobatae Radix group(YGG group), a medium-dose Puerariae Lobatae Radix group(YGZ group), and a low-dose Puerariae Lobatae Radix group(YGD group). Another 10 db/m mice were assigned to the normal group(K group). After continuous administration for eight weeks, body weight and blood sugar of mice were measured. Enzyme linked immunosorbent assay(ELISA) was used to detect glycosylated serum protein(GSP) and fasting serum insulin(FINS), and insulin resistance index(HOMA-IR) was calculated. The histopathological changes in the pancreas were observed by HE staining. Tumor necrosis factor(TNF)-α expression in the pancreas was detected using immunohistochemistry. The structural changes in fecal intestinal flora in the K, M, and YGZ groups were detected by 16S rRNA. Western blot was used to detect the expression of farnesoid X receptor(FXR) and takeda G protein-coupled receptor 5(TGR5) in the ileum, cholesterol 7α-hydroxylase(CYP7A1) and sterol 27α-hydroxylase(CYP27A1) in the liver, and G protein-coupled receptors 41(GPR41) and 43(GPR43) in the colon. Compared with the K group, the M group showed increased body weight, blood sugar, serum GSP, fasting blood glucose(FBG), and FINS, increased HOMA-IR, inflammatory infiltration of islet cells, necrosis and degeneration of massive acinar cells, unclear boundary between islet cells and acinar cells, disturbed intestinal flora, and down-regulated FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43. Compared with the M group, the YX, YGG, YGZ, and YGD groups showed decreased body weight, blood sugar, serum GSP, FBG, and FINS, islet cells with intact and clumpy morphology and clear boundary, necrosis of a few acinar cells, and more visible islet cells. The intestinal flora in the YGZ group changed from phylum to genus levels, and the relative abundance of intestinal flora affecting the metabolites of intestinal flora increased. The protein expression of FXR, TGR5, CYP7A1, CYP27A1, GPR41, and GPR43 increased. The results show that Puerariae Lobatae Radix can improve the inflammatory damage of pancreatic islet cells and reduce insulin resistance in db/db mice with T2DM. The mechanism of action may be related to the increase in the abundance of Actinobacteria, Bifidobacterium, and Bacteroides in the intestinal tract and the protein expression related to metabolites of intestinal flora.
Mice ; Animals ; Insulin Resistance ; Blood Glucose/metabolism* ; Diabetes Mellitus, Type 2/genetics* ; Pueraria/chemistry* ; Gastrointestinal Microbiome ; RNA, Ribosomal, 16S ; Body Weight ; Necrosis

In this study, insulin (insulin, INS)/Ca₃PO₄ complex and glucose oxidase (glucose oxidase, GOx)/Cu₃(PO₄)₂ complex were prepared by coprecipitation method. The mineralized insulin (mineralized insulin, m-INS) showed irregular crystalline clusters, and the mineralized glucose oxidase (m-GOx) showed flower spherical morphology, with a diameter of about 1-2 μm. In vitro simulated release experiment showed that m-INS released INS as the pH value of the medium decreased. When the pH value was 4.5, the release amount reached 96.68%. The enzyme activity detection experiment showed that the enzyme activity stability of m-GOx was higher than that of free GOx. It still maintained high activity after 10 days at room temperature, while the activity of GOx was less than 60%. The glucose solution was prepared to simulate the state of normal blood glucose (5.6 mmol/L) and hyperglycemia (22.2 mmol/L). When m-INS and m-GOx were added to the glucose solution, the release amount of INS showed a significant glucose concentration dependence. The higher the glucose concentration, the greater the release amount and release rate of INS. Finally, m-INS, m-GOx and hyaluronic acid (HA) solution were mixed to prepare HA microneedle arrays loaded with m-INS and m-GOx. Type 1 diabetes mice were constructed to evaluate the effect of drug-loaded HA microarray on blood glucose control in diabetic rats. The results show that the HA microneedles loaded with m-INS/m-GOx could deliver drugs effectively. The average blood glucose concentration in diabetic rats dropped to about 7 mmol/L within 1 h, normal blood glucose concentration could be maintained for 10 h, and the overall blood glucose concentration was lower than the level before administration for 36 hours. Compared with HA microneedles loaded with INS only, m-ins microneedles showed better glucose tolerance, longer-lasting glucose control effect and less risk of hypoglycemia. Compared with other sustained-release systems, the preparation process of the core components in this study is simple, efficient, safe and effective, and has great commercial potential.
Animals ; Blood Glucose ; Delayed-Action Preparations/therapeutic use* ; Diabetes Mellitus, Experimental/drug therapy* ; Drug Delivery Systems/methods* ; Glucose Oxidase/chemistry* ; Hyaluronic Acid ; I Blood-Group System ; Insulin/therapeutic use* ; Mice ; P Blood-Group System ; Rats

Animals ; Blood Glucose ; Diet, High-Fat/adverse effects* ; Fatty Liver/metabolism* ; Lipid Metabolism ; Lipids/blood* ; Liver/metabolism* ; Mice ; Mice, Knockout, ApoE ; Plant Extracts/pharmacology* ; Raphanus/chemistry* ; Seeds/chemistry*

BACKGROUND/OBJECTIVES: The glycemic index (GI) is a measure of the postprandial glucose response (PPGR) to food items, and glycemic load (GL) is a measure of the PPGR to the diet. For those who need to maintain a healthy diet, it is beneficial to regulate appropriate levels of blood glucose. In reality, what influences the meal GI or GL depends on the macronutrient composition and the physical chemistry reactions in vivo. Thus, we investigated whether different macronutrients in a meal significantly affect the PPGR and the validity of calculated GI and GL values for mixed meals. SUBJECTS/METHODS: 12 healthy subjects (6 male, 6 female) were recruited at a campus setting, and subjects consumed a total of 6 test meals one by one, each morning between 8:00 and 8:30 am after 12 h of fasting. PPGR was measured after each consumed meal and serial finger pricks were performed at indicated times. Test meals included 1) 68 g oral glucose, 2) 210 g rice, 3) rice plus 170 g egg white (RE), 4) rice plus 200 g bean sprouts (RS), 5) rice plus 10 g oil (RO), and 6) rice plus, egg white, bean sprouts, and oil (RESO). The incremental area under the curve (iAUC) was calculated to assess the PPGR. Mixed meal GI and GL values were calculated based on the nutrients the subjects consumed in each of the test meals. RESULTS: The iAUC for all meals containing two macronutrients (RS, RO, or RE) were not significantly different from the rice iAUC, whereas, the RESO iAUC (2,237.5 ± 264.9) was significantly lower (P < 0.05). The RESO meal's calculated GI and GL values were different from the actual GI and GL values measured from the study subjects (P < 0.05). CONCLUSIONS: The mixed meal containing three macronutrients (RESO) decreased the PPGR in healthy individuals, leading to significantly lower actual GI and GL values than those derived by nutrient-based calculations. Thus, consuming various macronutrient containing meals is beneficial in regulating PPGR.
Blood Glucose ; Chemistry, Physical ; Diet ; Egg White ; Fasting ; Fingers ; Glucose ; Glycemic Index ; Glycemic Load ; Healthy Volunteers ; Humans ; Male ; Meals

In 2018, external quality assessment trials for urinalysis and fecal occult blood (FOB) were performed using 1,590 participants. Urine chemistry tests were performed thrice while urine sediment and FOB tests twice. Urine chemistry tests comprised of pH, protein, glucose, ketone body, bilirubin, blood, urobilinogen, nitrite, leukocyte, and specific gravity analyses. The results of urine chemistry and specific gravity tests showed accuracy rates >95%, except for the pH test. The accuracy rate of urine sediments was low, especially for atypical calcium oxalate crystal and red blood cell cast. In the FOB quality test, reagents showed accuracy rates >90%, except for SD and GC Genedia FOB reagents. In the FOB quantitative test, Alfresa NS-Plus C instrument showed falsely high values in the FOB negative specimens.
Bilirubin ; Calcium Oxalate ; Chemistry ; Erythrocytes ; Glucose ; Hydrogen-Ion Concentration ; Indicators and Reagents ; Leukocytes ; Occult Blood ; Quality Control ; Specific Gravity ; Urinalysis ; Urobilinogen

Baihu Jia Renshen Decoction recorded in Treatise on Febrile Diseases by Zhang Zhongjing in the Han Dynasty could be used to clear heat,invigorate Qi,and promote fluid production. The indications of Baihu Jia Renshen Decoction include infectious diseases,such as lung infection,influenza,encephalitis,enteric typhoid and hospital infection; thermoplegia; acute cerebrovascular disease,diabetes mellitus,severe hyperosmolarity,hypernatremia,intractable hypotension,shock and other internal diseases; sweating,irritation,thirst,want to drink several liters of water,dry mouth,dry tongue,and big pulse. This prescription has been widely used to treat acute and severe cases in the cardiovascular intensive care ward. The prescription can be used to treat exogenous and internal injury diseases,which are characterized by excessive heat,fluid injury,thirst for water,dry mouth,dry tongue and other symptoms; refractory hypotension and hypovolemic shock that need large dose of supplemental fluid to maintain blood pressure and may also belong to the extension of the Baihu Jia Renshen Decoction formula syndrome; severe hyperosmolarity and hypernatremia needing nasal feeding with large quantities of sterile water or cool boiled water that may also belong to the extension of the Baihu Jia Renshen Decoction formula syndrome; the four major symptoms,namely severe heat,excessive perspiration,great thirst,and large-bounding pulse,are actually the indications of Baihu Jia Renshen Decoction,rather than Baihu Decoction. Severe irritability should also be added into the indications of Baihu Jia Renshen Decoction; severe heat refers to pathogenesis,rather than a symptom.
Blood Glucose/drug effects* ; Blood Pressure/drug effects* ; Critical Care ; Drugs, Chinese Herbal/pharmacology* ; Hot Temperature ; Humans ; Integrative Medicine ; Panax/chemistry* ; Phytotherapy ; Syndrome ; Treatment Outcome

Catalpol, a major bioactive component from Rehmannia glutinosa, which has been used to treat diabetes. The present study was designed to elucidate the anti-diabetic effect and mechanism of action for catalpol in db/db mice. The db/db mice were randomly divided into six groups (10/group) according to their blood glucose levels: db/db control, metformin (positive control), and four dose levels of catalpol treatment (25, 50, 100, and 200 mg·kg), and 10 db/m mice were used as the normal control. All the groups were administered orally for 8 weeks. The levels of fasting blood glucose (FBG), random blood glucose (RBG), glucose tolerance, insulin tolerance, and glycated serum protein (GSP) and the globe gene expression in liver tissues were analyzed. Our results showed that catalpol treatment obviously reduced water intake and food intake in a dose-dependent manner. Catalpol treatment also remarkably reduce fasting blood glucose (FBG) and random blood glucose (RBG) in a dose-dependent manner. The RBG-lowering effect of catalpol was better than that of metformin. Furthermore, catalpol significantly improved glucose tolerance and insulin tolerance via increasing insulin sensitivity. Catalpol treatment significantly decreased GSP level. The comparisons of gene expression in liver tissues among normal control mice, db/db mice and catalpol treated mice (200 and 100 mg·kg) indicated that there were significant increases in the expressions of 287 genes, whichwere mainly involved in lipid metabolism, response to stress, energy metabolism, and cellular processes, and significant decreases in the expressions of 520 genes, which were mainly involved in cell growth, death, immune system, and response to stress. Four genes expressed differentially were linked to glucose metabolism or insulin signaling pathways, including Irs1 (insulin receptor substrate 1), Idh2 (isocitrate dehydrogenase 2 (NADP), mitochondrial), G6pd2 (glucose-6-phosphate dehydrogenase 2), and SOCS3 (suppressor of cytokine signaling 3). In conclusion, catalpol ecerted significant hypoglycemic effect and remarkable therapeutic effect in db/db mice via modulating various gene expressions.
Animals ; Blood Glucose ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; genetics ; metabolism ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Drugs, Chinese Herbal ; administration & dosage ; analysis ; Gene Expression ; drug effects ; Glucosephosphate Dehydrogenase ; genetics ; metabolism ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Receptor Substrate Proteins ; genetics ; metabolism ; Iridoid Glucosides ; administration & dosage ; analysis ; Isocitrate Dehydrogenase ; genetics ; metabolism ; Liver ; drug effects ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Rehmannia ; chemistry ; Suppressor of Cytokine Signaling 3 Protein ; genetics ; metabolism

Diabetic nephropathy (DN) is one of the common microvascular complications of diabetes mellitus. Renal fibrosis is closely related to the deterioration of renal function. The present study aimed to investigate protective effect of Taxus chinensis on high-fat diet/streptozotocin-induced DN in rats and explore the underlying mechanism of action. The rat DN model was established via feeding high fat diet for 4 weeks and subsequently injecting streptozotocin (30 mg·kg body weight) intraperitoneally. The rats with blood glucose levels higher than 16.8 mmol·L were selected for experiments. The DN rats were treated with Taxus chinensis orally (0.32, 0.64, and 1.28 g·kg) once a day for 8 weeks. Taxus chinensis significantly improved the renal damage, which was indicated by the decreases in 24-h urinary albumin excretion rate, blood serum creatinine, and blood urea nitrogen. Histopathological examination confirmed the protective effect of Taxus chinensis. The thickness of glomerular basement membrane was reduced, and proliferation of mesangial cells and podocytes cells and increase in mesangial matrix were attenuated. Further experiments showed that Taxus chinensis treatment down-regulated the expression of TGF-β1 and α-SMA, inhibited phosphorylation of Smad2 and Smad3. These results demonstrated that Taxus chinensis alleviated renal injuries in DN rats, which may be associated with suppressing TGF-β1/Smad signaling pathway.
Albumins ; Animals ; Blood Glucose ; metabolism ; Creatinine ; blood ; Diabetic Nephropathies ; blood ; drug therapy ; genetics ; urine ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Kidney ; drug effects ; metabolism ; Male ; Phosphorylation ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Smad Proteins ; genetics ; metabolism ; Taxus ; chemistry ; Transforming Growth Factor beta1 ; metabolism

The present study compared active ingredients of tea from different sources to select tea type and the fraction of tea extracts for the highest anti-hyperglycemic activity, and to verify anti-hyperglycemic activity of the selected tea extract. Tea extracts were separated and enriched by molecular weight using ultra-filtration technology. The extracts were first screened by -glucosidase inhibition assay, followed by using a rat inverted intestine sac system to measure the effect on glucose transport. Both alloxan-induced diabetic rat model and high-fat diet combined with streptozotocin-induced rat diabetes mellitus model were used to study the effects of active components on blood glucose, body weight, insulin resistance. The experimental results showed that the different kinds of tea extracts had different inhibitory effects on -glucosidase, and the inhibitory effect of tea extract E on -glucosidase was stronger. The effects of different components of tea extract E also varied greatly, of which Fraction AN protein had stronger inhibitory effect on -glucosidase than other fragments, and Fraction AN protein had a strong inhibitory effect on glucose transport, reduced blood sugar and normalized insulin secretion in diabetic rats. The results suggest that a glycol-protein fraction(AN) from the extracts might be responsible for the anti-hyperglycemic activity of tea polysaccharides. The AN glycol-protein fraction has strong inhibitory effects on both -glucosidase activity and glucose transport by the small intestine. It also reduced blood glucose level and normalized insulin secretion in diabetic rats, and has a protective effect on diabetic rats.
Animals ; Blood Glucose ; Diabetes Mellitus, Experimental ; drug therapy ; Glycols ; pharmacology ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; pharmacology ; Plant Extracts ; chemistry ; Rats ; Tea ; chemistry ; alpha-Glucosidases

OBJECTIVE: To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy. METHODS: Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting. RESULTS: Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05). CONCLUSIONS Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.
Animals ; Autophagy ; drug effects ; Beclin-1 ; analysis ; Blood Glucose ; analysis ; Body Weight ; Diabetic Cardiomyopathies ; drug therapy ; pathology ; physiopathology ; Lipids ; blood ; Male ; Myocardium ; pathology ; Polyphenols ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tea ; chemistry