OBJECTIVE: To elucidate the effect of Huanglian-Renshen-Decoction (HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β -cell identity through regulating paracrine and endocrine glucagon-like peptide-1 (GLP-1)/GLP-1 receptor (GLP-1R) in both islet and intestine. METHODS: The db/db mice were divided into the model (distilled water), low-dose HRD (LHRD, 3 g/kg), high-dose HRD (HHRD, 6 g/kg), and liraglutide (400 µ g/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group (n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1 levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry (IHC) and immunofluorescence (IF) staining. Then, GLP-1, GLP-1R, prohormone convertase 1/3 (PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A (MafA), and pancreatic and duodenal homeobox 1 (PDX1) were detected by Western blot, IHC, IF, and real-time quantitative polymerase chain reaction, respectively. RESULTS: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time (P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon (P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass (P<0.01). After HRD treatment, the levels of GLP-1, GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased (P<0.05 or P<0.01). CONCLUSION HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.
Animals ; Glucagon-Like Peptide 1/metabolism* ; Diabetes Mellitus, Type 2/metabolism* ; Glucagon-Like Peptide-1 Receptor/metabolism* ; Insulin-Secreting Cells/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Blood Glucose/metabolism* ; Insulin/blood* ; Mice ; Intestinal Mucosa/pathology* ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Islets of Langerhans/pathology*

OBJECTIVES: To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms. METHODS: KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting. RESULTS: Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology. CONCLUSIONS LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals ; Mice ; Lipid Metabolism ; Diabetes Mellitus, Type 2/metabolism* ; Enterococcus faecium ; Glucagon-Like Peptide 1/metabolism* ; Bacillus subtilis ; Diabetes Mellitus, Experimental/metabolism* ; Circadian Rhythm ; Blood Glucose/metabolism* ; Receptors, G-Protein-Coupled/metabolism* ; Fatty Acids, Volatile/metabolism* ; Male ; Chronobiology Disorders/metabolism*

To explore the application value of serum Gal-13, GLP-1 and VEGF in the prevention and guidance of adverse pregnancy outcomes in gestational diabetes (GDM). A retrospective study with case-control method was used to select 1 012 GDM patients from Haikou Maternal and Child Health Hospital from January 2019 to December 2022 as the study objects, and they were divided into poor pregnancy outcome group (n=342) and good pregnancy outcome group (n=670) according to whether they had adverse pregnancy outcomes. The medical records of 521 healthy women with normal glucose metabolism were selected as the control group. Serum Gal-13 and GLP-1 were detected by enzyme-linked immunosorbent assay and VEGF was determined by IAMMGE specific protein analyzer. After comparing the differences of the above factors among the three groups, multivariate logistic regression model was used to analyze the influencing factors of adverse pregnancy outcomes in GDM patients, and ROC curve was drawn to analyze the predictive value of serum Gal-13, GLP-1 and VEGF levels on adverse pregnancy outcomes in GDM patients. The results showed that Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) in the adverse pregnancy outcome group were 5.92(4.98, 6.41) mmol/L, 5.32(4.96, 5.47)%, 62.56(49.21,99.50) pmol/L, VEGF was 495.47(389.14, 567.13) ng/L, TSH was 1.48(1.34, 1.58) mIU/L, right ventricular myocardial work index (Tei index) was 0.59(0.45, 0.67), 89 cases of elderly parturients; FPG was 4.45(4.16, 5.03) mmol/L, HbA1c was 5.04(4.86, 5.29)%, FINS was 57.41(46.90, 74.08) pmol/L, VEGF was 405.84(348.02, 462.68) ng/L, TSH was 1.42(1.25, 1.50) mIU/L, Tei index was 0.50(0.47, 0.64), there were 142 cases of old women. In the control group, FPG was 4.33(4.05, 4.75) mmol/L, HbA1c was 5.01(4.13, 5.18)%, FINS was 38.48(36.76, 41.72) pmol/L and VEGF was 302.45(283.14, 336.56) ng/L, TSH was 1.32(1.24, 1.47)mIU/L, Tei index was 0.48(0.39, 0.59), and there were 106 elderly parturiencies. The levels of FPG, HbA1c, FINS, VEGF, TSH and Tei index in the adverse pregnancy outcome group and the good pregnancy outcome group were higher than those in the control group, and the proportion of elderly parturients was higher than that in the control group, and the adverse pregnancy outcome group was higher than that in the good pregnancy outcome group. The differences were statistically significant (H=8.620, P<0.001, H=2.616, P=0.014, H=6.156, P<0.001, H=3.051, P<0.001, H=4.892, P=0.044, χ²=2.548, P=0.045). In the adverse pregnancy outcome group, Gal-13 was 15.27(8.35, 24.45)pg/ml, GLP-1 was 9.27(8.26, 12.35) pmol/L and FT4 was 11.59(9.67, 13.48) pmol/L. In the group with good pregnancy outcome, Gal-13 was 25.34(20.14, 29.73) pg/ml, GLP-1 was 12.38(10.25, 15.63) pmol/L and FT4 was 13.86(10.67, 15.10) pmol/L. In the control group, Gal-13 was 31.21(27.48, 34.45) pg/ml, GLP-1 was 11.34(10.40, 14.37) pmol/L and FT4 was 14.15(10.75, 15.43)pmol/L. The levels of Gal-13, GLP-1 and FT4 in the adverse pregnancy outcome group and the good pregnancy outcome group were significantly lower than those in the control group, and the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group. The differences were statistically significant (H=6.458, P=0.011, H=8.445, P<0.001, H=5.694, P<0.001). The levels of Gal-13 and GLP-1 in normal blood glucose recovery group were higher than those in non-normal blood glucose recovery group, and the levels of VEGF were lower than those in non-normal blood glucose recovery group (P<0.05).In multivariate logistic regression analysis, Gal-13, GLP-1, VEGF, TSH, FT4 and Tei indexes were independent influencing factors for adverse pregnancy outcomes with GDM (P<0.05). ROC curve analysis showed that the AUC of Gal-13, GLP-1 and VEGF alone in predicting adverse pregnancy were 0.779, 0.761 and 0.615, respectively. The value of the combined diagnosis was the highest (AUC=0.912), the sensitivity was 90.1%, and the specificity was 80.0%. In conclusion, Gal-13, GLP-1 and VEGF may be independent influencing factors for adverse pregnancy outcomes in GDM patients, and the combined detection of the three may help to improve the auxiliary diagnostic efficacy for predicting adverse pregnancy outcomes.
Aged ; Child ; Female ; Humans ; Pregnancy ; Blood Glucose ; Diabetes, Gestational ; Glucagon-Like Peptide 1 ; Glycated Hemoglobin ; Pregnancy Outcome ; Retrospective Studies ; Thyrotropin ; Vascular Endothelial Growth Factor A

To explore the application value of serum Gal-13, GLP-1 and VEGF in the prevention and guidance of adverse pregnancy outcomes in gestational diabetes (GDM). A retrospective study with case-control method was used to select 1 012 GDM patients from Haikou Maternal and Child Health Hospital from January 2019 to December 2022 as the study objects, and they were divided into poor pregnancy outcome group (n=342) and good pregnancy outcome group (n=670) according to whether they had adverse pregnancy outcomes. The medical records of 521 healthy women with normal glucose metabolism were selected as the control group. Serum Gal-13 and GLP-1 were detected by enzyme-linked immunosorbent assay and VEGF was determined by IAMMGE specific protein analyzer. After comparing the differences of the above factors among the three groups, multivariate logistic regression model was used to analyze the influencing factors of adverse pregnancy outcomes in GDM patients, and ROC curve was drawn to analyze the predictive value of serum Gal-13, GLP-1 and VEGF levels on adverse pregnancy outcomes in GDM patients. The results showed that Fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c) and fasting insulin (FINS) in the adverse pregnancy outcome group were 5.92(4.98, 6.41) mmol/L, 5.32(4.96, 5.47)%, 62.56(49.21,99.50) pmol/L, VEGF was 495.47(389.14, 567.13) ng/L, TSH was 1.48(1.34, 1.58) mIU/L, right ventricular myocardial work index (Tei index) was 0.59(0.45, 0.67), 89 cases of elderly parturients; FPG was 4.45(4.16, 5.03) mmol/L, HbA1c was 5.04(4.86, 5.29)%, FINS was 57.41(46.90, 74.08) pmol/L, VEGF was 405.84(348.02, 462.68) ng/L, TSH was 1.42(1.25, 1.50) mIU/L, Tei index was 0.50(0.47, 0.64), there were 142 cases of old women. In the control group, FPG was 4.33(4.05, 4.75) mmol/L, HbA1c was 5.01(4.13, 5.18)%, FINS was 38.48(36.76, 41.72) pmol/L and VEGF was 302.45(283.14, 336.56) ng/L, TSH was 1.32(1.24, 1.47)mIU/L, Tei index was 0.48(0.39, 0.59), and there were 106 elderly parturiencies. The levels of FPG, HbA1c, FINS, VEGF, TSH and Tei index in the adverse pregnancy outcome group and the good pregnancy outcome group were higher than those in the control group, and the proportion of elderly parturients was higher than that in the control group, and the adverse pregnancy outcome group was higher than that in the good pregnancy outcome group. The differences were statistically significant (H=8.620, P<0.001, H=2.616, P=0.014, H=6.156, P<0.001, H=3.051, P<0.001, H=4.892, P=0.044, χ²=2.548, P=0.045). In the adverse pregnancy outcome group, Gal-13 was 15.27(8.35, 24.45)pg/ml, GLP-1 was 9.27(8.26, 12.35) pmol/L and FT4 was 11.59(9.67, 13.48) pmol/L. In the group with good pregnancy outcome, Gal-13 was 25.34(20.14, 29.73) pg/ml, GLP-1 was 12.38(10.25, 15.63) pmol/L and FT4 was 13.86(10.67, 15.10) pmol/L. In the control group, Gal-13 was 31.21(27.48, 34.45) pg/ml, GLP-1 was 11.34(10.40, 14.37) pmol/L and FT4 was 14.15(10.75, 15.43)pmol/L. The levels of Gal-13, GLP-1 and FT4 in the adverse pregnancy outcome group and the good pregnancy outcome group were significantly lower than those in the control group, and the adverse pregnancy outcome group was lower than that in the good pregnancy outcome group. The differences were statistically significant (H=6.458, P=0.011, H=8.445, P<0.001, H=5.694, P<0.001). The levels of Gal-13 and GLP-1 in normal blood glucose recovery group were higher than those in non-normal blood glucose recovery group, and the levels of VEGF were lower than those in non-normal blood glucose recovery group (P<0.05).In multivariate logistic regression analysis, Gal-13, GLP-1, VEGF, TSH, FT4 and Tei indexes were independent influencing factors for adverse pregnancy outcomes with GDM (P<0.05). ROC curve analysis showed that the AUC of Gal-13, GLP-1 and VEGF alone in predicting adverse pregnancy were 0.779, 0.761 and 0.615, respectively. The value of the combined diagnosis was the highest (AUC=0.912), the sensitivity was 90.1%, and the specificity was 80.0%. In conclusion, Gal-13, GLP-1 and VEGF may be independent influencing factors for adverse pregnancy outcomes in GDM patients, and the combined detection of the three may help to improve the auxiliary diagnostic efficacy for predicting adverse pregnancy outcomes.
Aged ; Child ; Female ; Humans ; Pregnancy ; Blood Glucose ; Diabetes, Gestational ; Glucagon-Like Peptide 1 ; Glycated Hemoglobin ; Pregnancy Outcome ; Retrospective Studies ; Thyrotropin ; Vascular Endothelial Growth Factor A

In 2018, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) published a consensus recommendation on management of hyperglycemia. This consensus report emphasized the need for patient-centered management considering multimorbidity and individual patient preferences and barriers. Patients with type 2 diabetes with established atherosclerotic cardiovascular disease who fail to control blood glucose with the initial glucose-lowering medication are recommended a sodium-glucose cotransporter 2 (SGLT2) inhibitor or a glucagon-like peptide 1 (GLP-1) receptor agonist. For patients with chronic kidney disease and heart failure, SGLT2 inhibitors are recommended. In patients who need an injectable medication, GLP-1 receptor agonists are the preferred choice over insulin. In this section, we summarize “Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).”
Atherosclerosis ; Blood Glucose ; Cardiovascular Diseases ; Comorbidity ; Consensus ; Diabetes Mellitus ; Glucagon-Like Peptide 1 ; Glucagon-Like Peptide-1 Receptor ; Heart Failure ; Humans ; Hyperglycemia ; Insulin ; Patient Preference ; Patient-Centered Care ; Renal Insufficiency, Chronic

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

BACKGROUND/OBJECTIVES: Mulberry leaf (ML) has been shown to have an inhibitory effect on α-glucosidase, and suppresses postprandial hyperglycemia, which may be related to its deoxynojirimycin (DNJ) content. This study was conducted to investigate the hypoglycemic and dyslipidemic effects of rice coated with ML rich in DNJ in a type 2 diabetes mouse model. MATERIALS/METHODS: The mice were divided into four groups (n = 8 each): non-diabetic normal control (NC); diabetic control (DM-C), fed with 10% polished rice powder (DM-R); and fed with 10% polished rice powder coated with DNJ-rich ML (DM-DNJR). RESULTS: Supplementation with DNJR for six weeks decreased levels of fasting blood glucose, plasma insulin, triglyceride, total cholesterol, and blood glycosylated hemoglobin; conversely, levels of glucagon-like peptide-1 and high-density lipoprotein-cholesterol showed an increase in the same treatment. In addition, weights of mesenteric, epididymal, and total adipose tissues decreased with DNJR supplementation, when compared with diabetic control db/db mice, while maltase, lactase, and sucrase activity in the small intestine were inhibited. The anti-diabetic effects were marginally greater in the DM-DNJR group than in the DM-R group. CONCLUSIONS: These results suggest that rice coated with ML rich in DNJ can reduce hyperglycemia and hyperlipidemia in db/db mice, and may prove useful for individuals with diabetes.
Animals ; Blood Glucose ; Cholesterol ; Diabetes Mellitus ; Dyslipidemias* ; Fasting ; Glucagon-Like Peptide 1 ; Hemoglobin A, Glycosylated ; Hyperglycemia* ; Hyperlipidemias ; Hypoglycemia ; Insulin ; Intestine, Small ; Lactase ; Mice* ; Morus* ; Plasma ; Sucrase ; Triglycerides ; Weights and Measures

One of the new promising therapies in treatment of diabetes mellitus is mesenchymal stem cells (MSCs) which have an interesting therapeutic potentiality based on their paracrine effect and transdifferentiation potentiality. Also obestatin improves the generation of functional β cells/islet-like cell clusters in vitro, suggesting implications for cell-based replacement therapy in diabetes. So the aim of this study was to evaluate the effect of combination of both MSCs and obestatin on an experimental model of type II diabetes mellitus (T2DM). Sixty male rats were divided into; group I (control group), group II (T2DM group) induced by administration of high fat diet (HFD) and injection of streptozotocin (STZ) in low dose, group III (T2DM treated with MSCs), group IV (T2DM treated with obestatin), group V (T2DM treated with MSCs and obestatin). Fasting blood glucose, C-peptide, insulin and lipid profile were measured. HOMA-IR and HOMA-β were calculated. Pancreatic expression of insulin, glucagon like peptide -1 (GLP-1) and pancreatic duodenal homeobox 1 (Pdx1) mRNA levels were measured. In addition pancreatic histological changes, insulin and Bax were analyzed by immunohistochemical examination of islets of Langerhans. Diabetic rats showed significant increase in HOMA-IR, serum glucose and lipid profile levels with significant decrease in insulin, HOMA-β, GLP-1 and Pdx1 levels. MSCs and obestatin caused significant improvement in all parameters with more significant improvement in combined therapy. The protective effects afforded by MSCs and obestatin may derive from improvement of the metabolic profile, antiapoptosis and by increase in pancreatic GLP-1and Pdx1 gene expression.
Animals ; Blood Glucose ; Bone Marrow* ; C-Peptide ; Diabetes Mellitus ; Diet, High-Fat ; Fasting ; Gene Expression ; Genes, Homeobox ; Ghrelin* ; Glucagon ; Glucagon-Like Peptide 1 ; Humans ; In Vitro Techniques ; Insulin ; Islets of Langerhans ; Male ; Mesenchymal Stromal Cells* ; Metabolome ; Models, Theoretical ; Rats* ; RNA, Messenger ; Streptozocin

To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms.Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg·d), low-dose berberine group (30 mg·kg·d), moderate-dose berberine group (60 mg·kg·d), and high-dose berberine group (120 mg·kg·d). All animals were fed for 3 d, and fasting blood sampling was performed on day 3 of administration. Rats were given glucose (2 g/kg) by gavage 30 min after the last dose. Blood and intestinal samples were obtained 2 h after glucose loading. Fasting blood glucose (FBG) and 2-h postprandial plasma glucose (2h-PPG) were detected by using biochemical analyzer, and insulin, glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-Ⅳ(DPP-Ⅳ) were measured by using ELISA kit.No significant difference in FBG and serum DPP-Ⅳ level were found between berberine groups and control group (all>0.05). Compared with control group, serum levels of GLP-1 and insulin were increased in high-and moderate-dose berberine groups, while 2h-PPG was decreased (all<0.05); GLP-1 levels in the intestinal samples were increased, while DPP-Ⅳ levels were decreased in all berberine groups (all<0.05).Short-term berberine administration can decrease 2h-PPG level in streptozotocin-induced diabetic rat model through local inhibition of intestinal DPP-Ⅳ. The efficacy of DPP-Ⅳ inhibitor may be associated with its intestinal pharmacokinetics.
Animals ; Berberine ; pharmacokinetics ; pharmacology ; Blood Glucose ; drug effects ; Diabetes Mellitus, Experimental ; chemically induced ; drug therapy ; Dipeptidyl Peptidase 4 ; analysis ; drug effects ; pharmacokinetics ; Dipeptidyl-Peptidase IV Inhibitors ; Dose-Response Relationship, Drug ; Glucagon-Like Peptide 1 ; analysis ; blood ; Hypoglycemic Agents ; Insulin ; blood ; Intestines ; chemistry ; drug effects ; Male ; Rats ; Rats, Sprague-Dawley ; Sitagliptin Phosphate

Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).
Adult ; Aged ; Area Under Curve ; Blood Glucose/*analysis ; Cross-Over Studies ; Diabetes Mellitus, Type 2/complications/diagnosis/*diet therapy ; Dietary Fiber/*therapeutic use ; Female ; Gastric Inhibitory Polypeptide/blood ; Glucagon/blood ; Glucagon-Like Peptide 1/*blood ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hyperglycemia/complications/diagnosis ; Insulin/blood ; Intestines/metabolism ; Male ; Middle Aged ; ROC Curve