Humans ; Glucagon-Like Peptide-1 Receptor/agonists* ; Diabetic Cardiomyopathies/drug therapy* ; Diabetes Mellitus, Type 2

OBJECTIVES: To explore the effects of somatostatin on the levels of gastrointestinal hormones and clinical outcomes in critically ill infants after gastrointestinal surgery. METHODS: Using a random number table method, critically ill infants after gastrointestinal surgery who were admitted to the Intensive Care Unit of Xuzhou Children's Hospital from June 2019 to June 2021 were randomly divided into an observation group (29 cases) and a control group (30 cases). The control group received routine treatment such as anti-infection and hemostasis after surgery, while the observation group received somatostatin in addition to the routine treatment [3.5 μg/(kg·h) infusion for 7 days]. The levels of serum gastrin (GAS), motilin (MTL), insulin, and glucagon-like peptide-1 (GLP-1) before surgery, on the 3rd day after surgery, and on the 7th day after surgery were compared between the two groups. The recovery progress and incidence of complications after surgery were also compared between the two groups. RESULTS: There was no significant difference in the levels of serum GAS, MTL, insulin, and GLP-1 between the two groups before surgery (P>0.05). On the 3rd and 7th day after surgery, the levels of serum GAS, MTL, insulin, and GLP-1 in the observation group were higher than those in the control group (P<0.05). In the observation group, the levels of GAS, MTL, insulin, and GLP-1 on the 7th day after surgery were higher than those before surgery and on the 3rd day after surgery (P<0.05), and the levels on the 3rd day after surgery were higher than those before surgery (P<0.05). There was no significant difference in the levels of serum GAS, MTL, and insulin before surgery, on the 3rd day after surgery, and on the 7th day after surgery in the control group (P>0.05). The level of GLP-1 on the 7th day after surgery was higher than that before surgery and on the 3rd day after surgery (P<0.05), and the level on the 3rd day after surgery was higher than that before surgery (P<0.05) in the control group. The observation group had shorter first time of anal exhaust, recovery time of bowel sounds, and first time of defecation after surgery compared to the control group (P<0.05). The incidence of complications after surgery in the observation group was lower than that in the control group (10% vs 33%, P<0.05). CONCLUSIONS Somatostatin can increase the levels of serum GAS, MTL, insulin, and GLP-1 in critically ill infants after gastrointestinal surgery, promote the recovery of gastrointestinal function, and reduce the incidence of postoperative complications.
Humans ; Infant ; Critical Illness ; Digestive System Surgical Procedures ; Glucagon-Like Peptide 1 ; Insulin ; Prospective Studies ; Somatostatin/therapeutic use*

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

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.
Mice ; Animals ; Glucagon-Like Peptide 1/metabolism* ; Receptors, Glucagon/therapeutic use* ; Xenopus laevis/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Glycopeptides/therapeutic use* ; Obesity/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Peptides/pharmacology*

Type 2 diabetes is a high-profile global public health problem, particularly in Asia. The young age of onset, low body mass index, and early appearance of pancreatic islet dysfunction are characteristics of Asian patients with T2DM. Metabolic surgery has become the standard treatment for T2DM patients and can significantly improve T2DM through a variety of mechanisms including modulation of energy homeostasis and reduction of body fat mass. Indeed, restoration of islet function also plays an integral role in the remission of T2DM. After metabolic surgery, islet function in Asian T2DM patients has improved significantly, with proven short-term and long-term effects. In addition, islet function is an important criterion and reference for patient selection prior to metabolic surgery. The mechanism of islet function improvement after metabolic surgery is not clear, but postoperative anatomical changes in the gastrointestinal tract leading to a number of hormonal changes seem to be the potential cause, including glucagon-like peptide-1, gastric inhibitory polypeptide, peptide YY, ghrelin, and cholecystokinin. The authors analyzed the current retrospective and prospective studies on the effect of metabolic surgery on the islet function of Asian T2DM patients with a low BMI and its mechanism, summarized the clinical evidence that metabolic surgery improved islet function in Asian T2DM patients with a low BMI, and discussed its underlying mechanism. It is of great significance for realizing personalized and precise treatment of metabolic surgery and further improving its clinical benefits.
Bariatric Surgery ; Body Mass Index ; Cholecystokinin/therapeutic use* ; Diabetes Mellitus, Type 2/surgery* ; Gastric Inhibitory Polypeptide/therapeutic use* ; Ghrelin/therapeutic use* ; Glucagon-Like Peptide 1/therapeutic use* ; Humans ; Peptide YY/therapeutic use* ; Prospective Studies ; Retrospective Studies ; Treatment Outcome

Obesity is an important risk factor of type 2 diabetes (T2D), which has become an important factor threatening human health. However, no perfect drug choice for obesity exists. Semaglutide is a kind of human glucagon-like peptide-1 (GLP-1) analog that promotes insulin secretion while inhibiting glucagon secretion through a glucose concentration-dependent mechanism. GLP-1 can also delay stomach emptying and suppress appetite to help lose weight. This review summarizes clinical evidence of the semaglutide effect on T2D and obesity and establishes expectations on future clinical trials for obesity treatment.
Diabetes Mellitus, Type 2/drug therapy* ; Glucagon-Like Peptide-1 Receptor/therapeutic use* ; Glucagon-Like Peptides ; Humans ; Hypoglycemic Agents/therapeutic use* ; Motivation ; Obesity/drug therapy*

AMP-Activated Protein Kinases/metabolism* ; Adenosine ; Adenosine Monophosphate ; Cell Proliferation ; Endometrial Neoplasms/drug therapy* ; Female ; Humans ; Liraglutide ; Phosphorylation ; Protein Kinases ; Signal Transduction

OBJECTIVE: To study the effect of exendin-4(Ex-4) on the differentiation of neural stem cells(NSCs) in adult mouse subventricular zone(SVZ)and its mechanism . METHODS: NSCs in the SVZ were derived from 5-week C57BL/6J mice and the expression of nestin was detected by immunofluorescence. The cell morphology was observed after the cells treatmed with 100 nmol/L Ex-4 for 14 days.The expressions of nestin and glucagon-like peptide-1 receptor (GLP-1R) were detected by immunofluorescence. GLP-1R was knocked down by using shRNA and the study was divided into four groups: control group, Ex-4 group, GLP-1R knockdown group, GLP-1R knockdown + Ex-4 group. After treatment with 100 nmol/L Ex-4 for 14 d, β-tublin III and glial fibrillary acidic protein (GFAP) were labeled by immunofluorescence and then the proportion of β-tublin III positive cells were counted. Western blot was used to detect the activation of cAMP-response element binding protein (CREB) in NSCs. In order to further study the effects of Ex-4 on mitogen-activated protein kinase(MAPK) and phosphatidylinositol 3-hydroxy kinase (PI3K) pathways, the cells were pretreated with MAPK inhibitor U0126 at a concentration of 0.07 μmol/L for 30 min or PI3K inhibitor LY294002 at 50 μmol for 2 h, respectively. The study was divided into six groups: control group, Ex-4 group, U0126 group, U0126 + Ex-4 group, LY294002 group, LY294002 + Ex-4 group. The activation of CREB in each group was detected by Western blot. The experiment was repeated three times independently. RESULTS: NSCs were successfully extracted from SVZ of C57BL/6J mice. Immunofluorescence showed that nestin and GLP-1R were positive in NSCs. Compared with the control group, the proportion of neurons differentiated from Ex-4 group was higher. The percentage of neurons in GLP-1R knockdown + Ex-4 group was basically the same as that in control group (P＜0.01). The positive cells of beta-tublin III showed positive activation of GLP-1R and CREB. Western blot showed that CREB was significantly activated in the Ex-4 group, and knockdown of GLP-1R abolished its activation (P＜0.01). U0126 did not affect Ex-4-mediated CERB activation, and LY294002 significantly reduced Ex-4-mediated CREB activation (P＜0.01). CONCLUSION Ex-4 promotes the differentiation of NSCs into neurons in SVZ of adult mice through GLP-1R receptor, which may be achieved through PI3K/CREB pathway.
Animals ; Cell Differentiation ; Cells, Cultured ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Exenatide ; pharmacology ; Gene Knockdown Techniques ; Glucagon-Like Peptide-1 Receptor ; genetics ; metabolism ; Lateral Ventricles ; cytology ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells ; cytology ; Phosphatidylinositol 3-Kinases

Glucagon-like peptide-1 (GLP-1) expression is shared by both intestinal cells and neurons of brainstem, which plays anorexigenic role on food intake. However, the exact source of physiological GLP-1 influencing food intake and pertinent mechanism of GLP-1 receptor agonists (GLP-1RA) remain unelucidated. In this study, the immediate early gene product c-Fos was chosen as the specific antigen for immunohistochemistry to show the certain areas of central nervous system (CNS) activation by the GLP-1RA. Thirty normal SD rats were randomly assigned to 3 groups, which were single intraperitoneally injected with Liraglutide (200 μg/kg), Exenatide (10 μg/kg) and saline, respectively. After injection, the amount of food intake and acute glycemic variation were assessed for comparison. The results showed that acute pharmacological dosage of GLP-1RA (Liraglutide or Exenatide) could significantly influence food intake. However, glycemic change indicated that the anorexic effect was dissociated with change in blood glucose in normal rats. Moreover, c-Fos was expressed significantly higher in major critical nuclei related to food intake in GLP-1RA groups when compared with the control group, and its expression was also found in spinal cord. The results suggested that acute administration of pharmacological doses of GLP-1 influences CNS via circulation and vagal pathways, especially on the arcuate nucleus (ARC) and the nucleus of solitary tract (NTS), and GLP-1 modulates autonomic nervous activities.
Animals ; Eating ; drug effects ; Exenatide ; pharmacology ; Glucagon-Like Peptide-1 Receptor ; agonists ; Liraglutide ; pharmacology ; Random Allocation ; Rats ; Rats, Sprague-Dawley