cholecystokinin and Diabetes-Mellitus--Type-1

The biological clock mechanism was studied in both non-insulin-dependent and insulin-dependent diabetic model rats. Otsuka Long Evans Tokushima Fatty (OLETF) rats were used as a non-insulin-dependent model. Streptozotocin (STZ, 100 mg/kg, i.p.) was administered to 8- to 10-week-old Wistar rats for an insulin-dependent diabetic model. Both young non-diabetic OLETF and STZ-induced diabetic rats needed more days for re-entrainment to a new light-dark cycle than control rats on activity rhythm. In young OLETF rats, dim-light-induced Fos expression (50 and 100 lux) was significantly decreased in the suprachiasmatic nucleus. In diabetic OLETF rats, Fos expression was decreased by the exposure of light at 300 lux. In STZ-induced diabetic rats, Fos expression was also decreased by 300 lux of light. In OLETF rats, the phase delay by glutamate application was significantly smaller than that in control rats on the suprachiasmatic nucleus neuronal (SCN) activity rhythms. On the other hand, the same level of phase delay was observed between control and STZ-induced diabetic rats by glutamate application. These results suggest that entrainment function is disordered in OLETF rats before the onset of hyperglycemia. To clarify the entrainment function of STZ-induced diabetic rats, however, further study is necessary.

Topics: Animals; Biological Clocks; Cholecystokinin; Circadian Rhythm; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Models, Animal; Motor Activity; Proto-Oncogene Proteins c-fos; Rats; Rats, Inbred OLETF; Rats, Wistar; Serotonin; Streptozocin; Suprachiasmatic Nucleus

Topics: Acute Disease; Amylases; Bicarbonates; Cholecystokinin; Chronic Disease; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Humans; Insulin; Islets of Langerhans; Lipase; Middle Aged; Pancreas; Pancreatic Juice; Pancreatitis; Secretin

Recent randomized and controlled trials of drugs derived from the gut hormone glucagon-like peptide-1 (GLP-1) show that the most frequent adverse symptoms are gastrointestinal, including gallbladder-related side effects such as cholithiasis and cholecystitis. Since the gut hormone cholecystokinin (CCK) stimulates bile secretion and regulates gallbladder motility and emptying, we examined the effect of GLP-1 on the secretion of CCK in normal subjects and patients with type 1 diabetes mellitus.. Plasma was sampled from 10 healthy subjects and 10 patients with diabetes. With plasma glucose concentrations clamped between 6 and 9 nmol/l, GLP-1 or saline was infused for 240 min during and after a meal. The plasma concentrations of CCK were measured with a highly specific radioimmunoassay.. Basal plasma concentrations of CCK were similar in the normal subjects and in the diabetes patients. During the meal, the CCK concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of CCK significantly in both normal subjects and in the diabetes patients.. The results show that GLP-1 suppresses the secretion of CCK after a meal in normal and diabetic subjects. The suppression attenuates the gallbladder contractility. Our data, therefore, offer an explanation for the increased risk of adverse gallbladder events during treatment with GLP-1-derived drugs.

Topics: Adult; Blood Glucose; Case-Control Studies; Cholecystokinin; Diabetes Mellitus, Type 1; Female; Gallbladder; Gallbladder Emptying; Glucagon-Like Peptide 1; Humans; Male; Young Adult

Topics: Animals; Cholecystokinin; Diabetes Mellitus, Type 1; Drug Design; Female; Humans; NADP; Second Messenger Systems; Uterine Contraction

In patients with chronic pancreatitis (CP) the relation among exocrine pancreatic secretion, gastrointestinal hormone release, and motility is disturbed. We studied digestive and interdigestive antroduodenal motility and postprandial gut hormone release in 26 patients with CP. Fifteen of these patients had pancreatic insufficiency (PI) established by urinary para-aminobenzoic acid test and fecal fat excretion. Antroduodenal motility was recorded after ingestion of a mixed liquid meal. The effect of pancreatic enzyme supplementation was studied in 8 of the 15 CP patients with PI. The duration of the postprandial antroduodenal motor pattern was significantly (P < 0.01) prolonged in CP patients (324 +/- 20 min) compared with controls (215 +/- 19 min). Antral motility indexes in the first hour after meal ingestion were significantly reduced in CP patients. The interdigestive migrating motor complex cycle length was significantly (P < 0.01) shorter in CP patients (90 +/- 8 min) compared with controls (129 +/- 8 min). These abnormalities were more pronounced in CP patients with exocrine PI. After supplementation of pancreatic enzymes, these alterations in motility reverted toward normal. Digestive and interdigestive antroduodenal motility are abnormal in patients with CP but significantly different from controls only in those with exocrine PI. These abnormalities in antroduodenal motility in CP are related to maldigestion.

Topics: Adult; Aged; Cholecystokinin; Chronic Disease; Diabetes Mellitus, Type 1; Digestion; Duodenum; Eating; Enzymes; Female; Gastrointestinal Motility; Humans; Islets of Langerhans; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Pancreatitis; Peptide YY

Hyperglycaemia slows gastric emptying in both normal subjects and patients with diabetes mellitus. The mechanisms mediating this effect, particularly the potential role of insulin, are uncertain. Hyperinsulinaemia has been reported to slow gastric emptying in normal subjects during euglycaemia. The purpose of this study was to evaluate the effect of euglycaemic hyperinsulinaemia on gastric emptying in Type I (insulin-dependent) and Type II (noninsulin-dependent) diabetes mellitus. In six patients with uncomplicated Type I and eight patients with uncomplicated Type II diabetes mellitus, measurements of gastric emptying were done on 2 separate days. No patients had gastrointestinal symptoms or cardiovascular autonomic neuropathy. The insulin infusion rate was 40 mU x m(-2) x min(-1) on one day and 80 mU x m(-2) x min(-1) on the other. Gastric emptying and intragastric meal distribution were measured using a scintigraphic technique for 3 h after ingestion of a mixed solid/liquid meal and results compared with a range established in normal volunteers. In both Type I and Type II patients the serum insulin concentration had no effect on gastric emptying or intragastric meal distribution of solids or liquids. When gastric emptying during insulin infusion rates of 40 mU x m(-2) x min(-1) and 80 mU x m(-2) x min(-1) were compared the solid T50 was 137.8+/-24.6 min vs. 128.7+/-24.3 min and liquid T50 was 36.7+/-19.4 min vs. 40.4+/-15.7 min in the Type I patients; the solid T50 was 94.9+/-19.1 vs. 86.1+/-10.7 min and liquid T50 was 21.8+/-6.9 min vs. 21.8+/-5.9 min in the Type II patients. We conclude that hyperinsulinaemia during euglycaemia has no notable effect on gastric emptying in patients with uncomplicated Type I and Type II diabetes; any effect of insulin on gastric emptying in patients with diabetes is likely to be minimal.

Topics: Adult; Amyloid; Blood Glucose; C-Peptide; Cholecystokinin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Gastric Emptying; Glucagon; Glucagon-Like Peptide 1; Glucose Clamp Technique; Glycated Hemoglobin; Humans; Hyperinsulinism; Hypoglycemic Agents; Infusions, Intravenous; Insulin; Islet Amyloid Polypeptide; Male; Peptide Fragments; Protein Precursors

Patients with diabetes mellitus are at increased risk of developing gallstones. This has been attributed, among other factors, to alterations in gallbladder motility in the presence of autonomic neuropathy. Since high blood glucose concentrations impair gastric emptying in diabetic patients, we have investigated the effect of acute hyperglycaemia on gallbladder motility. Seven Type 1 (insulin-dependent) diabetic patients were studied twice during euglycaemia (blood glucose 5 mmol/l) and hyperglycaemia (blood glucose 15 mmol/l) using a clamp technique. In addition, seven healthy volunteers were studied during euglycaemia and hyperglycaemia. Gallbladder volumes, measured with ultrasonography, were studied before and during infusion of step-wise increasing doses of cholecystokinin-33, 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1, each dose for 30 min. Mean basal gallbladder volumes were not significantly different in the four experiments. Administration of cholecystokinin resulted in significant (p < 0.05) dose-dependent reductions in gallbladder volume in all experiments. During euglycaemia the gallbladder contraction in diabetic patients was not significantly different from the control subjects. During hyperglycaemia the gallbladder contraction in the diabetic patients was significantly (p < 0.05) reduced compared to euglycaemia only during infusion of 0.25 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (19 +/- 6% vs 33 +/- 6%). Compared to euglycaemia, during hyperglycaemia the gallbladder contraction in the control subjects was significantly (p < 0.05) reduced during infusion of 0.25, 0.5 and 1.0 Ivy Dog Unit.kg-1.h-1 of cholecystokinin (14 +/- 4% vs 31 +/- 3%; 42 +/- 6% vs 65 +/- 5%; 74 +/- 4% vs 90 +/- 3%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Glucose; Cholecystokinin; Diabetes Mellitus, Type 1; Female; Gallbladder; Glucagon; Glucose Clamp Technique; Humans; Hyperglycemia; Infusions, Intravenous; Male; Muscle Contraction; Muscle, Smooth; Pancreatic Polypeptide; Reference Values; Ultrasonography

Pancreozymin-secretin-stimulated secretion was measured for volume, bicarbonate concentration and total amylase output in 16 noninsulin-dependent patients and 23 age-, sex-, and weight-matched similar control subjects. Another group of 17 insulin-dependent patients was studied using secretin stimulation and the secretory response compared to a similar group of 37 control subjects. Pancreozymin-secretin-stimulated pancreatic function was normal in noninsulin-dependent patients. Abnormal values for at least one parameter of secretion were found in 82% of insulin-dependent patients. Amylase output was low in 35% and bicarbonate concentration was low in 30%. Hypersecretion occurred in 35%. One patient had abnormal values for all three parameters and three patients had two abnormal values. Hypersecretory response to secretin stimulation is considered to be an early finding of pancreatic exocrine dysfunction among insulin-dependent patients. Progressive secretory failure occurs as the pathological process increases, and a decrease in total amylase output becomes the most significant abnormality.

Topics: Adolescent; Adult; Aged; Amylases; Bicarbonates; Cholecystokinin; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Humans; Male; Middle Aged; Pancreas; Pancreatic Function Tests; Secretin; Thailand

Exocrine pancreatic function was evaluated in 19 diabetic children on the basis of a pancreozymin-secretin test, a p-aminobenzoic acid (PABA) test, and a determination of fasting plasma trypsin and elastase-1 levels. In the pancreozymin-secretin test, the diabetics exhibited lower mean values in all the parameters measured, significant differences being seen in the volume of duodenal fluid and the output of bicarbonate and amylase. Compared to the controls, the diabetics also had lower levels in the PABA test and in the trypsin and elastase-1 measurements. No significant correlation was seen between exocrine pancreatic dysfunction and the duration of diabetes. However, the duration of diabetes in children who showed extremely low levels (below the mean +/- 2 SD for the control subjects) in the PABA test and low plasma trypsin and elastase-1 values was more than 1 year. This study revealed that diabetic children had reduced exocrine pancreatic function, some in an early stage of the disease. Therefore, the reduction may be due to a functional disturbance rather than to an anatomical loss of exocrine pancreatic tissue.

Topics: 4-Aminobenzoic Acid; Adolescent; Child; Child, Preschool; Cholecystokinin; Diabetes Mellitus, Type 1; Fasting; Female; Humans; Male; Pancreas; Pancreatic Elastase; Secretin; Trypsin

Topics: Adolescent; Adult; Cholecystokinin; Diabetes Mellitus; Diabetes Mellitus, Type 1; Humans; Middle Aged; Pancreas; Pancreatic Function Tests; Secretin

Topics: Amylases; Blood Glucose; Cholecystokinin; Diabetes Mellitus; Diabetes Mellitus, Type 1; Glycosuria; Isoenzymes; Pancreas; Salivary Glands; Secretin

Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.

Topics: Adolescent; Adult; Amylases; Bicarbonates; C-Peptide; Cholecystokinin; Diabetes Mellitus, Type 1; Female; Glucagon; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Male; Middle Aged; Pancreas; Secretin; Trypsin

Exocrine pancreatic function was studied in 20 juvenile-onset diabetics, seven maturity-onset diabetics, and five patients with diabetes secondary to chronic pancreatitis. The results were compared with 13 non-diabetic controls. The outputs of bicarbonate, trypsin, and amylase were reduced in the diabetic patients in response to intravenous secretin and CCK-PZ. In the juvenile-onset group, exocrine pancreatic secretory capacity was reduced in 80% of the patients, and the severity of the reduction was related to the duration of the diabetes. The reduction in pancreatic secretory capacity must be taken into consideration when interpreting pancreatic exocrine function in patients with diabetes.

Topics: Adolescent; Adult; Amylases; Bicarbonates; Cholecystokinin; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Middle Aged; Pancreas; Secretin; Stimulation, Chemical; Time Factors; Trypsin

In 11 juvenile diabetics and 13 control subjects, the secretin-pancreozymin test was performed. Duodenal-volume losses were corrected by use of radioactive vitamin B12 as marker substance. As compared to normal subjects, juvenile diabetics had significantly decreased pancreatic outputs of amylase, trypsin, chymotrypsin, and to a lesser degree, of bicarbonate. Clinical evidence of disease of the exocrine pancreas was missing. There was no discernible relationship between the abnormality of external pancreatic function and the duration of diabetes mellitus or the dose of insulin required. Possible factors that may be responsible for the exocrine deficiency of the pancreas in juvenile diabetics are discussed.

Topics: Adult; Amylases; Animals; Bicarbonates; Cholecystokinin; Chymotrypsin; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Insulin; Male; Pancreas; Pancreatic Juice; Rats; Secretin; Trypsin; Vitamin B 12

Topics: Cholecystokinin; Diabetes Mellitus, Type 1; Gastrectomy; Humans; Pancreas; Pancreatic Diseases; Pancreatitis; Secretin; Stimulation, Chemical

Topics: Adolescent; Adult; Amylases; Bicarbonates; Cholecystokinin; Chronic Disease; Chymotrypsin; Clinical Enzyme Tests; Cobalt Radioisotopes; Diabetes Mellitus, Type 1; Female; Humans; Injections, Intravenous; Lipase; Male; Pancreatic Diseases; Pancreatitis; Proteins; Secretin; Trypsin; Vitamin B 12

Topics: Acute Kidney Injury; Adult; Amino Acids; Amylases; Cholecystokinin; Diabetes Mellitus, Type 1; Diabetic Nephropathies; Duodenum; Female; Glucose; Humans; Kidney Transplantation; Lipase; Pancreas; Pancreas Transplantation; Renal Dialysis; Transplantation, Homologous; Trypsin; Trypsin Inhibitors

Topics: Adolescent; Amylases; Blood Chemical Analysis; Cholecystokinin; Diabetes Mellitus; Diabetes Mellitus, Type 1; Gastrointestinal Hormones; Humans; Insulin; Lipase; Pancreatic Juice; Pancreatic Neoplasms; Pancreatitis; Secretin