glucagon-like-peptide-1 and Stomach-Neoplasms

The purpose of this study is to compare the effect of diabetes control induced by Roux-en-Y gastrojejunostomy(RY) vs Billroth-I reconstruction(BI) after distal gastrectomy in patients with early gastric cancer(EGC) and type 2 diabetes(T2DM). Forty EGC patients with T2DM, aged 20-80 years, who were expected to undergo curative distal gastrectomy were randomized 1:1 to RY(n = 20) or BI(n = 20). Diabetes medication status, biochemical and hormonal data including blood glucose, HbA1c, insulin, C-peptide, HOMA-IR, ghrelin, leptin, GLP-1, PYY, and GIP were evaluated for 12 months after surgery. Although pre- and postoperative 12-month fasting and postprandial glucose levels did not show a significant difference, HbA1c, C-peptide, and HOMA-IR levels were significantly improved at 12 months after surgery in both BI and RY groups. Sixty percent of RY patients and 20% of BI patients decreased their medication satisfying FBS<126 mg/dL and HbA1c<6.5% and 5% of BI patients stopped their medication satisfying the criteria of FBS<126 mg/dL and HbA1c<6.0%. The improvement patterns were more sustainable with less fluctuation in RY than in BI. On hormonal analysis, ghrelin and leptin levels were decreased and PYY and GIP levels were increased at 12 months after surgery in both groups without significant difference according to the reconstruction type and diabetic improvement status except ghrelin. In gastric cancer surgery, RY reconstruction showed better and more durable diabetes control compared to BI during the first year after surgery. Gastric cancer surgery led to decreased ghrelin and leptin and increased PYY and GIP, which might have a role in improving insulin resistance and glucose homeostasis.

Topics: Aged; Diabetes Mellitus, Type 2; Duodenum; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Ghrelin; Glucagon-Like Peptide 1; Humans; Leptin; Male; Middle Aged; Peptide YY; Prospective Studies; Stomach; Stomach Neoplasms; Treatment Outcome

The present study aimed to investigate changes in glucose metabolism and incretin hormone response following longer intestinal bypass reconstruction after distal gastrectomy (DG) in low BMI patients with gastric cancer and type 2 diabetes. A total of 20 patients were prospectively recruited and underwent either conventional Billroth I (BI), Billroth II with long-biliopancreatic limb (BII), or Roux-en-Y anastomosis with long-Roux limb (RY) after DG. A 75g-oral glucose tolerance test (OGTT) was given preoperatively; and at 5 days, 3 months, and 6 months postoperatively. Serum glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were serially measured. At 6 months after surgery, complete diabetes remission was achieved in 57.1% of the BII group but in no patients in the other two groups (p = 0.018). BII group showed a significant reduction in glucose concentration during OGTT at 6 months in contrast to the other 2 groups. In the BII group, a significant increase in GLP-1 secretion was observed after surgery but not maintained at 6 months, while postoperative hyperglucagonemia was alleviated along with a reduction in GIP. BII gastrojejunostomy with long biliopancreatic limb achieved better diabetes control with favorable incretin response after DG compared to BI or RY reconstruction.

Topics: Aged; Anastomosis, Roux-en-Y; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Female; Follow-Up Studies; Gastrectomy; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Incretins; Insulin; Male; Middle Aged; Postoperative Period; Prospective Studies; Stomach Neoplasms; Treatment Outcome

Dumping syndrome is a frequent and potentially severe complication after gastric surgery. Beinaglutide, a recombinant human glucagon-like peptide-1 (GLP-1) which shares 100% homology with human GLP-1(7-36), has never been reported in the treatment of dumping syndrome before.. The patient had undergone distal gastrectomy for gastric signet ring cell carcinoma 16 months ago. He presented with symptoms of paroxysmal palpitation, sweating, and dizziness for 4 months.. He was diagnosed with late dumping syndrome.. The patient was treated with dietary changes and acarbose for 4 months before admitted to our hospital. The treatment with dietary changes and acarbose did not prevent postprandial hyperinsulinemia and hypoglycemia according to the 75 g oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM) on admission.Therefore, the patient was treated with beinaglutide 0.1 mg before breakfast and lunch instead of acarbose. After the treatment of beinaglutide for 1 month, OGTT showed a reduction in postprandial hyperinsulinemia compared with before starting treatment, and the time in the range of 3.9 to 10 mmol/L became 100% in CGM. No side effect was observed in this patient during beinaglutide treatment.. These findings suggest that beinaglutide may be effective for treating post-gastrectomy late dumping syndrome.

Topics: Blood Glucose; Carcinoma, Signet Ring Cell; Dumping Syndrome; Gastrectomy; Glucagon-Like Peptide 1; Glucose Tolerance Test; Humans; Hyperinsulinism; Hypoglycemia; Male; Middle Aged; Peptide Fragments; Postprandial Period; Recombinant Proteins; Stomach Neoplasms; Treatment Outcome

Decrease in appetite and weight after total gastrectomy in patients with gastric cancer leads to a decrease in quality of life, increased mortality, and may necessitate discontinuation of adjuvant chemotherapy. The aim of this study is to determine whether rikkunshito, a Japanese herbal medicine, increases food intake and weight after gastrectomy in rats.. Male rats underwent gastrectomy followed by roux-en-Y reconstruction or sham operation and were then treated with rikkunshito for 14 days starting on postoperative day 3. Daily food intake, weight, plasma glucagon-like peptide-1 (GLP-1), and ghrelin levels were measured. A pilot study to measure pre- and postoperative plasma GLP-1 levels was conducted in patients who underwent total gastrectomy for gastric cancer.. Administration of rikkunshito after gastrectomy in rats significantly increased food intake and weight, which continued for at least 2 weeks after treatment. Both fasting and postprandial plasma GLP-1 levels were increased markedly after gastrectomy compared with sham-operated animals. Increased GLP-1 levels in rats after gastrectomy were suppressed markedly by rikkunshito. rikkunshito had no significant effect on plasma ghrelin levels after gastrectomy. Treatment with a GLP-1 receptor antagonist significantly improved food intake and weight after gastrectomy. Plasma fasting GLP-1 levels in patients with gastric cancer were increased greatly after gastrectomy on postoperative day 1.. Administration of rikkunshito suppresses plasma GLP-1 levels after total gastrectomy, which is associated with recovery from reduced food intake and weight in rats.

Topics: Animals; Appetite; Biomarkers; Drug Administration Schedule; Drugs, Chinese Herbal; Eating; Gastrectomy; Gastrointestinal Agents; Ghrelin; Glucagon-Like Peptide 1; Humans; Male; Pilot Projects; Postoperative Care; Rats; Rats, Wistar; Stomach Neoplasms; Weight Loss

Roux-en-Y gastric bypass (RYGB) is effective in controlling blood glucose in obese patients with type 2 diabetes (T2DM). The alterations of gut hormones involving in glucose metabolism may play an important role. Our aim was to explore the short-term effects of Billroth II gastrojejunostomy (a similar type of RYGB) on glucose metabolism and gut hormone modulations in nonobese patients with different levels of blood glucose tolerance.. Twenty one nonobese gastric cancer patients with different levels of blood glucose tolerance were submitted to Billroth II gastrojejunostomy. Among them, seven had T2DM, seven with impaired glucose tolerance (IGT) and the other seven had normal glucose tolerance (NGT). Body weight, glucose parameters, responses of plasma glucagon-like peptide-1 (GLP-1), peptide YY (PYY) and gastric inhibitory polypeptide (GIP) to 75 g glucose were measured at baseline and 3 months after surgery.. Similar weight losses were observed in all groups. Blood glucose was reduced in T2DM and IGT patients. Fasting and 30-min plasma glucose were increased significantly in NGT. GLP-1 showed insignificant alterations in all groups. PYY was evaluated in T2DM and IGT but remained unchanged in the NGT group. Decreased fasting and AUC GIP were observed in patients with T2DM; however, fasting and 30-min GIP were increased in NGT patients.. Billroth II gastrojejunostomy is effective in reducing blood glucose in nonobese patients with T2DM and IGT but could deteriorate early blood glucose in nonobese NGT in a 3-month time period. Variations of glucose and gut hormone changes in the three groups suggest a role of proximal intestine in the pathophysiology of T2DM.

Topics: Adult; Aged; Area Under Curve; Blood Glucose; Diabetes Mellitus, Type 2; Female; Gastric Bypass; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose Intolerance; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Insulin; Male; Middle Aged; Obesity; Peptide YY; Postoperative Period; Stomach Neoplasms; Weight Loss

Intestinal metaplasia (IM) in the human stomach has previously been classified into a gastric and intestinal mixed (GI-IM) and a solely intestinal phenotype (I-IM). The phenotypes of mucous and endocrine cells were evaluated in 3034 glandular ducts associated with chronic gastritis. In the pyloric region, the relative expression of gastric endocrine cell markers, such as gastrin and somatostatin, decreased gradually from glandular ducts with only gastric mucous cell phenotype (G type) to GI-IM toward I-IM, while that of the intestinal endocrine cell markers, glicentin, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) was inversely correlated. In the fundic region, gastrin-positive cells emerged in the pseudo-pyloric and GI-IM glands, whereas I-IM glands did not possess any gastrin-positive cells, suggesting the presence of a distinct pathway of intestinalization. Double staining revealed coexistence of gastrin- and GLP-1-positive cells in the same gland and occasionally in the same cell in GI-IM glands. These results suggest that the phenotypes of endocrine cells are in line with those for mucous counterparts and support the concept that all of the different types of mucous and endocrine cells in normal and IM glands might be derived from a single progenitor cell in each gland.

Topics: Aged; Chromogranin A; Chromogranins; Endocrine Glands; Female; Gastric Fundus; Gastric Inhibitory Polypeptide; Gastric Mucosa; Gastrins; Glicentin; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Humans; Immunohistochemistry; Intestines; Male; Metaplasia; Middle Aged; Peptide Fragments; Protein Precursors; Pyloric Antrum; Somatostatin; Stomach Neoplasms

Exaggerated plasma concentrations of GLP-1 precede reactive hypoglycemia after oral glucose in gastrectomy patients, resulting in late dumping syndrome. Recently, we showed that GLP-1 elicits the activation of sympathetic outflow. Because sympathetic activation is thought to be a cause of early dumping, we hypothesized that exaggerated GLP-1 may contribute to the pathophysiology of early dumping syndrome. In 11 patients after gastrectomy and 14 controls, blood pressure, heart rate, and plasma concentrations of norepinephrine, epinephrine, GLP-1, glucagon, insulin, and glucose were measured after oral glucose. In gastrectomy patients, GLP-1, norepinephrine, and heart rate peaked 15 to 30 min after oral glucose. Significant positive correlations were found among GLP-1, norepinephrine, and heart rate at 30 min, and these parameters at 30 min were significantly higher in patients with early dumping syndrome. These results suggest that GLP-1 is involved in the pathophysiology of early dumping syndrome.

Topics: Adult; Analysis of Variance; Biomarkers; Blood Glucose; Case-Control Studies; Catecholamines; Dumping Syndrome; Female; Gastrectomy; Glucagon-Like Peptide 1; Hemodynamics; Humans; Insulin; Linear Models; Male; Middle Aged; Prognosis; Reference Values; Risk Assessment; Sensitivity and Specificity; Severity of Illness Index; Stomach Neoplasms

The HGT-1 gastric cancer cell line was used to determine the actions of protein kinase C on the stimulation of adenylate cyclase by the human histamine H2 receptor, and the receptors for gastric inhibitory polypeptide and truncated glucagon like peptide 1 (TGLP-1). Suspensions of HGT-1 cells were preincubated with the activator of protein kinase C, 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/l), for 10 minutes. The subsequent cyclic adenosine monophosphate (AMP) response to 0.5 mmol/l histamine or 100 nmol/l TGLP-1 was reduced by comparison with control cells preincubated in the absence of TPA. The cyclic AMP response to 100 nmol/l gastric inhibitory polypeptide was enhanced by preincubation with TPA, while the responses to cholera toxin and forskolin were unaffected. Preincubation with pertussis toxin prevented the enhancement of the gastric inhibitory polypeptide response by TPA, suggesting an involvement of an inhibitory guanine nucleotide regulatory subunit of the Gi class, but did not change the inhibition of histamine stimulation. In conclusion, activation of protein kinase C produces a specific inhibition of the effects of histamine and TGLP-1 on adenylate cyclase activity in a human gastric cancer cell line by acting at a site close to their receptors.

Topics: Adenylate Cyclase Toxin; Adenylyl Cyclases; Alkaloids; Cyclic AMP; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Histamine; Humans; Peptide Fragments; Pertussis Toxin; Protein Kinase C; Protein Precursors; Receptors, Gastrointestinal Hormone; Receptors, Histamine H2; Staurosporine; Stimulation, Chemical; Stomach Neoplasms; Tetradecanoylphorbol Acetate; Tumor Cells, Cultured; Virulence Factors, Bordetella

We tested the truncated 7-37 glucagon-like peptide 1 (TGLP-1), a naturally occurring porcine intestinal peptide, and other members of the glucagon family, including pancreatic glucagon (G-29), GLP-1 and GLP-2 for their ability to activate the cAMP generating system in rat gastric glands and HGT-1 human gastric cancer cells. In rat fundic glands, TGLP-1 was about 100 times more potent (EC50 = 2.8 X 10(-9) M) than GLP-1 of G-29, and 10 times more potent than G-29 in the HGT-1 cell line. Our results support the notion that TGLP-1 plays a direct role in the regulation of acid secretion in rat and human gastric mucosa.

Topics: Animals; Cyclic AMP; Gastric Mucosa; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor; Humans; Male; Peptides; Protein Precursors; Rats; Receptors, Cell Surface; Receptors, Glucagon; Stomach Neoplasms; Tumor Cells, Cultured