OBJECTIVETo observe postoperative glucose tolerance, gastric inhibitory polypeptide (GIP) , and glucogan-like peptide-1 (GLP-1) in normal glucose level dogs after undergoing gastric bypass procedures, and to explore the mechanism of gastric bypass procedures to treat type 2 diabetes.

METHODSThe 6 dogs with normal glucose tolerance had undergone gastric bypass procedures, and measure preoperative and postoperative oral and intravenous glucose tolerance (at time points 1, 2, and 4 weeks) through changes in blood glucose, insulin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and measure preoperative and postoperative week 4 pancreatic tissue morphology.

RESULTSSecond weeks after operation, the fasting blood sugar was (3.58 ± 0.33) mmol/L, and significantly lower than preoperative (t = 3.571, P < 0.05). The GLP-1 level before oral glucose tolerance test (OGTT) and 30 minutes after OGTT were (0.90 ± 0.21) and (0.91 ± 0.19) pmol/L respectively, and significantly higher than preoperative (t value were -3.660 and -2.971, P < 0.05). GLP-1 levels began to decrease in the second week after surgery. After 4 weeks, the index recovered to the preoperative level. Four weeks after surgery when compared with preoperative, islet morphology, islet number (6.8 ± 0.8 and 7.1 ± 0.8 respectively) and islet cells (16.7 ± 2.5 and 16.3 ± 3.1 respectively) did not change significantly (P > 0.05).

CONCLUSIONGastric bypass procedures could be briefly affect normal glucose tolerance in dogs' blood glucose, insulin and diabetes-related gastrointestinal hormones.

Animals ; Blood Glucose ; Diabetes Mellitus, Type 2 ; Dogs ; Gastric Bypass ; Gastric Inhibitory Polypeptide ; Glucagon ; Glucagon-Like Peptide 1 ; blood ; Glucose ; Insulin ; blood

OBJECTIVETo investigate the secretion patterns of glucose-dependent insulinotropic polypeptide (GIP) after different dietary loads in subjects with normal glucose tolerance (NGT) and their relation to insulin secretion and plasma glucose levels.

METHODSFourteen subjects with normal glucose tolerance underwent 75 g glucose tolerance test(OGTT) followed by mixed meal tolerance test(MMT) one week later. Blood glucose, insulin, and GIP were measured in the fasting state and at 0, 15, 30, 60, 90 and 120 min after glucose load or mixed meal load.

RESULTSThe first peak value of GIP after glucose load occurred at 15 min (45.09∓4.67 pmol/L). After a brief decline, GIP continued to increase till reaching 59.66∓11.73 pmol/L at 120 min after the load. After the mixed meal load, GIP secretion presented with two peaks: the first peak appeared at 15 min (71.69∓14.19 pmol/L) with a level significantly higher than that at 15 min following glucose load (P<0.05), and the second occurred at 90 min (55.35∓13.19 pmol/L). The area under curve of GIP showed no significant difference between the two loads (P>0.05). Compared with glucose load, mixed meal load resulted in an increase of the first GIP peak and an earlier insulin peak (30 min vs 60 min), but a significant decrease of blood glucose at 15 min (P<0.05).

CONCLUSIONCompared with glucose load, mixed meal (containing fat) can strongly stimulate GIP release and cause earlier occurrence of the insulin peak, which might be an important reason for the lower blood glucose after mixed meal.

Adult ; Blood Glucose ; metabolism ; China ; ethnology ; Diet ; Energy Intake ; Female ; Gastric Inhibitory Polypeptide ; secretion ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Male ; Middle Aged ; Young Adult

BACKGROUND: K-cells function as targets for insulin gene therapy. In a previous study, we constructed EBV-based plasmids expressing rat preproinsulin controlled by glucose-dependent insulinotropic polypeptide promoters. In the present study, we attempted to correct hyperglycemia in vivo using genetically engineered K-cells in a mouse model of type 1 diabetes. METHODS: K-cells expressing insulin were transplanted under the kidney capsules of STZ-induced diabetic mice. The blood glucose levels and body weights of the experimental animals were measured daily. After four weeks, the mice were injected intra-peritoneally with 2 g/kg glucose following a 6 hr fast. Blood glucose levels were measured immediately following glucose injections. All animals were sacrificed at the end of the glucose tolerance study, and pancreas and graft-bearing kidney tissue samples were stained with antibodies against insulin, glucagon, and C-peptide. RESULTS: The body weights of K-cell-transplanted diabetic mice increased after transplantation, whereas those of untreated diabetic control mice continued to decline. The blood glucose levels of K-cell-transplanted diabetic mice decreased gradually during the two weeks following transplantation. After intra-peritoneal injection of glucose into K-cell-transplanted diabetic mice, blood glucose levels increased at 30 minutes, and were restored to the normal range between 60 and 90 minutes, while untreated control diabetic mice continued to experience hyperglycemia. Kidney capsules containing transplanted K-cells were removed, and sections were stained with anti-insulin antibodies. We detected insulin-positive cells in the kidney capsules of K-cell-transplanted diabetic mice, but not in untreated control mice. CONCLUSION: We detected glucose-dependent insulin secretion in genetically engineered K-cells in a mouse model of type 1 diabetes. Our results suggest that genetically modified insulin producing K-cells may act as surrogate beta-cells to effectively treat type 1 diabetes.
Animals ; Antibodies ; Blood Glucose ; Body Weight ; C-Peptide ; Capsules ; Gastric Inhibitory Polypeptide ; Genetic Therapy ; Glucagon ; Glucose ; Herpesvirus 4, Human ; Hyperglycemia ; Insulin ; Kidney ; Mice ; Pancreas ; Plasmids ; Protein Precursors ; Rats ; Reference Values ; Transplants

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

OBJECTIVE: To observe the clinical efficacy of sitagliptin plus insulin on patients with brittle diabetes and to determine the effect of the combined therapy on glucagon secretion.
 METHODS: This randomized, double-blinded and placebo-controlled trial included 30 patients with brittle diabetes. Participants were randomly assigned (1:1) to receive the treatment of either sitagliptin plus insulin or placebo plus insulin for 12 weeks. The blood glucose, hemoglobin A1c, insulin dose, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and other parameters were determined.
 RESULTS: After 12 weeks of treatment, blood glucose was controlled better by sitagliptin plus insulin (P<0.01). The patients had significantly lower glucose variability indices, lower daily insulin requirement and hemoglobin A1c in the group of sitagliptin plus insulin (P<0.01). After steamed bun test, past-meal GLP-1 levels at 30 min were higher (P<0.01) while GIP levels were lower (P<0.01), with glucagon suppression in the sitagliptin plus insulin group. No significant change was observed at any time point in placebo plus insulin group.
 CONCLUSION Sitagliptin significantly decreases blood glucose level and blood glucose fluctuation, which may contribute to the ability of sitagliptin in decreasing glucagon secretion.
Blood Glucose ; analysis ; C-Peptide ; blood ; Diabetes Mellitus, Type 1 ; drug therapy ; Dipeptidyl-Peptidase IV Inhibitors ; Double-Blind Method ; Drug Therapy, Combination ; Gastric Inhibitory Polypeptide ; blood ; Glucagon ; blood ; Glucagon-Like Peptide 1 ; blood ; Glycated Hemoglobin A ; analysis ; Humans ; Hypoglycemic Agents ; administration & dosage ; therapeutic use ; Insulin ; administration & dosage ; therapeutic use ; Sitagliptin Phosphate ; administration & dosage ; therapeutic use