The effect of hypophysectomy and hypophysis-transplantation on the secretion of gut glucagon immunoreactivity and gut glucagon-like immunoreactivity in depancreatized dogs

The role of hypophysis in the regulation mechanism of the secretion of gut glucagon immunoreactivity (gut GI) that was measured using C-terminal specific glucagon antiserum after pancreatectomy, and gut glucagon-like immunoreactivity (gut GLI) that was obtained by subtracting GI from total glucagon-like immunoreactivity (total GLI) which was measured using non-specific glucagon antiserum, was investigated in depancreatized dogs. Plasma glucose, gut GI and gut GLI levels were found to increase in totally depancreatized dogs. The former two showed a significant decrease after hypophysectomy, and were reversed by the hypophysis-transplantation, while gut GLI was not affected either by hypophysectomy or hypophysis-transplantation. Intramuscular injections of human growth hormone (HGH) or adrenocorticotropic hormone-Z (ACTH-Z) to depancreatized-hypophysectomized dogs had no effect on plasma glucose level or gut GI. It is concluded that hypophysis may promote the secretion of gut GI after pancreatectomy, but not of gut GLI. Gut GI seems to regulate plasma glucose level after pancreatectomy. However, the precise regulation mechanism of gut GI by the hypophysial hormone after pancreatectomy is not clarified yet.     

Effect of phenformin on the response of plasma intestinal glucagon-like immunoreactivity (GLI) to oral glucose in gastrectomized subjects.

The effect of phenformin (DBI) on the plasma intestinal glucagon-like immunoreactivity (GLI) and pancreatic glucagon (IRG) responses to oral and intravenous glucose loads were studied in 26 gastrectomized subjects, using a cross-reacting and an IRG-specific anti-serum. The drug produced no significant changes in fasting GLI and IRG levels. Thirty minutes after oral glucose alone, the total GLI level rose to a peak of 1.55 +/- 0.17 ng/ml in the untreated subjects and to a maximum level of 1.67 +/- 0.18 ng/ml in the DBI-pretreated subjects. However, the mean GLI levels obtained 120 and 180 min after oral glucose were significantly higher after treatment with DBI. The blood sugar and IRI responses to oral glucose were lowered significantly by DBI pretreatment. DBI did not alter the glucose, IRI, IRG and GLI response to intravenous glucose. These results suggest that the release of intestinal GLI is not related to the intestinal absorption of glucose.     

Oral administration of somatostatin reduces postprandial plasma triglycerides, gastrin and gut glucagon-like immunoreactivity.

The present study was designed to determine if orally administered somatostatin can reduce the postprandial rise in plasma triglycerides, gastrin, gut glucagon-like immunoreactivity (GLI) and the pancreatic hormones insulin and glucagon. Ten overnight fasted dogs were fed a fat-protein meal with or without 2 mg synthetic somatostatin, followed by another 2 mg somatostatin 90 min later. After the meal with somatostatin, postprandial plasma triglyceride levels were significantly lower for 5 hours, GLI levels for 3.5 hours and gastrin levels for 1 hour compared to the controls. Plasma insulin, glucagon and somatostatin-like immunoreactivity was not different from the control experiments. It is concluded that orally administered somatostatin lowers the postprandial levels of triglycerides, GLI and gastrin in dogs. This may have therapeutic implications for the management of gastrointestinal and metabolic disorders.     

Effects of amino-acids on pancreatic hormones and gut glucagon-like immunoreactivity in the goose

In the goose, alanine and arginine, intravenously or orally administered, act in the same way on pancreatic hormones; they both stimulate insulin and glucagon secretions. Conversely, whereas alanine treatment has no effect on plasma gut GLI, oral arginine stimulates gut GLI secretion. Since stimulation of gut GLI secretion does not occur with i.v. arginine, it may be assumed that this secretion depends on the intestinal transit of arginine and, as already described (Sitbon and Mialhe 1979), of glucose. The results, compared with studies on a similar species (duck) and on mammals, point out that i.v. infusion of alanine stimulates IRI and GLI secretions in the goose and not in the duck. In the same way, arginine i.v. infusion, contrarily to the observation made in the duck, is without effect on gut GLI secretion in the goose. Furthermore, insulin seems to be able to inhibit the alpha cell response to arginine infusion, as in mammals, whereas this is not the case in ducks.     

Effect of insulin on the response of gut glucagon-like immunoreactivity (GLI) to oral glucose and food ingestion in the goose

Gut GLI levels were measured in the plasma of normal, totally and subtotally depancreatized geese, using an antiserum specific for avian pancreatic glucagon and another one which crossreacts with intestinal extracts. Gut GLI was determined by difference between "total" GLI and immunoreactive pancreatic glucagon (IRG). Glucose given orally or a meal rich in carbohydrates elicited an elevation in plasma gut GLI. The increment of gut GLI was greater when the pancreas was removed. The over-stimulation of gut GLI was corrected by the administration of insulin. This is the first study which reports a correlation between insulin and gut GLI secretion in birds.     

Effect of exercise training on insulin and glucagon release from perfused rat pancreas

The effect of physical training on insulin and glucagon release in perfused rat pancreas was examined in the spontaneously exercised group running in a wheel cage an average of 1.4 km/day for 3 weeks and in the sedentary control group kept in the cage whose rotatory wheel was fixed on purpose. Pancreatic immunoreactive insulin (IRI) responses to glucose and arginine were reduced by 28% and 47.8% respectively in trained rats compared with untrained rats, while IRI content of the pancreas was similar in these two groups. The demonstrated decrease in insulin secretion of the beta-cell of the trained rats, in response to the glucose and arginine stimulations, may be functional in nature. On the other hand, neither pancreatic glucagon immunoreactivity (GI) response to glucose and arginine nor GI content of the pancreas was modified by exercise training. These results demonstrate that exercise training reduces IRI responses to glucose as well as to arginine stimulations, but does not modify any secretory response of pancreatic GI.     

Carbohydrate metabolism is not impaired after 3 years of growth hormone therapy in children with Prader-Willi syndrome

BACKGROUND/AIM: In children with Prader-Labhart-Willi syndrome (PWS), the insulin secretion is reduced, despite obesity, being ascribed to the growth hormone (GH) deficiency of hypothalamic origin. Besides, an increased prevalence of diabetes mellitus was described in this syndrome. Hence, we addressed the questions of how body composition and insulin secretion are interrelated and what impact GH therapy has on the carbohydrate metabolism in PWS. METHODS: We measured weight, lean and fat mass (by dual-energy X-ray absorptiometry), triglycerides, HbA(1c), and fasting insulin and glucose levels in 17 children (age range 1.5-14.6 years) with PWS to examine whether the carbohydrate metabolism is altered during 36 months of therapy with 8 mg GH/m(2) body surface/week. In a subgroup of 8 children, the insulin secretion was longitudinally assayed during oral glucose tolerance at 0 and 12 months of therapy. RESULTS: Before therapy, the insulin secretion was lower and markedly delayed as compared with reference data and did not rise during therapy. The glucose tolerance was impaired in 2 of 12 children examined by oral glucose tolerance test before therapy and normalized during therapy. Fasting insulin and insulin resistance being normal at the beginning, significantly increased at 12 months and returned to initial levels at 36 months of GH therapy. Fasting glucose as well as HbA(1c) and triglyceride levels were always normal. The fat mass before GH therapy was increased (39.5%) and dropped into the upper normal range (28.3%) during 3 years of therapy, being correlated with fasting insulin concentration and indices of insulin sensitivity before and after 1 year of therapy. CONCLUSIONS: Children with PWS are characterized by an intact insulin sensitivity with a decrease and a delay of insulin secretion, regardless of moderate obesity or GH treatment. In the present setting, the carbohydrate metabolism is not impaired by GH therapy, but by the excessively increased fat mass.     

Inhibition of pentagastrin-stimulated gastric acid secretion by intraileal administration of bile and elevation of plasma concentrations of gut glucagon-like immunoreactivity in anesthetized dogs

The effects of intraileal administration of bile on gastric acid secretion stimulated by a submaximal dose of intravenous pentagastrin infusion and on plasma concentrations of gut glucagon-like immunoreactivity (gut GLI) were studied in anesthetized dogs. Gastric acid secretion was measured for a 2-h period at 15-min intervals before and after intraluminal instillation of test solutions. 100 ml of canine bladder bile diluted to 10% in saline evoked a significant inhibition (20%) of gastric acid secretion. The inhibition of gastric acid secretion was accompanied by an elevation of plasma concentration of gut GLI, whereas saline instillation (in controls) caused no responses. Although the inhibition of gastric acid secretion and the elevation of plasma gut GLI are parallel phenomena, gut GLI can be reasonably postulated as one of the candidate mediators of bile-induced inhibition of gastric acid secretion, since its structurally related peptides, pancreatic glucagon, glicentin and oxyntomodulin have been reported as inhibitors of gastric acid secretion.     

Glucose, insulin, pancreatic glucagon and glucagon-like immunoreactive materials in the plasma of normal and diabetic children. Effect of the initial insulin treatment.

Pancreatic glucagon (PG) and other glucagon-like immunoreactive materials (GLI) were measured in the plasma of normal and of newly diagnosed untreated diabetic children, using an antiglucagon serum (AGS) highly specific for pancreatic glucagon (AGS 18) and an AGS which crossreacts with extracts of intestinal mucosa (AGS 10). Gut GLI was considered to be the difference between "total" GLI (AGS 10) and PG (AGS 18). Glucose and immunoreactive insulin (IRI) were also measured. PG, total GLI and gut GLI were significantly elevated in children with severe insulin insufficiency and were reduced to normal by insulin treatment, even though a significant fasting hyperglycemia was still present. In three diabetic children who had high initial plasma IRI levels the three glucagon fractions were normal. We conclude that insulin insufficiency is characterized not only by high plasma levels of PG as previously reported, but also of gut GLI. These abnormalities can be corrected by the administration of insulin.     

Glucose tolerance and insulinemia in patients with hepatic cirrhosis and portal hypertension treated by portacaval anastomosis]

Development of diabetes mellitus is a common complication of side to side porta-caval anastomosis (PCA). Five patients with liver cirrhosis and portal hypertension have been studied with intravehous (IVGTT, 0,5 g/Kg B.W.) and oral (OGTT, 1 g/Kg B.W.) glucose tolerance tests before and three weeks after PCA. Fasting plasma glucose was 84 +/- 7 before and 87 +/- 3 mg/dl after PCA. Fasting IRI increased from 17 +/- 3 to 31 +/- 6 microU/ml. The pattern of plasma glucose and IRI response to IVGTT did not change after PCA. Plasma glucose resonse to OGTT after PCA showed only an earlier rise at 60 instead of 90 minutes, whereas IRI resonse (area under the insulin curve) was significantly enhanced (from 12.4 to 19.8 U/l, p < 0.05). These data suggest a role of gut polipeptides in determining hyperinsulinemia and insulin resistence in PCA patients.     

Pancreatic hormones and plasma glucose: regulation mechanisms in the goose under physiological conditions. I. Pancreatectomy and replacement therapy

Measurements of plasma GLI and IRI in normal fasting geese, before and during constant I.V. infusion of saline, gave GLI/I ratios of 1.32 +/- .07 and 1.34 +/- .03 (w/w). As total pancreatectomy markedly reduces the pancreatic hormone level, leading to a mortal hypoglycaemia, we attempted to maintain plasma glucose within the normal range by constant I.V. infusion of glucagon and insulin into operated animals. The results as follows: 1. Blood glucose levels can be maintained within the normal range during experiments lasting 6 or more hours with a constant G/I ratio. 2. The G/I ratio obtained in operated animals (.96 +/- .12) is near to, but significantly lower (p less than .005) than, the GLI/I ratio measured in normal animals. This difference may be explained by the presence of a small amount of circulating gut GLI in the 2nd group.     

Reduction of C-peptide secretion in noninsulin-dependent diabetic patients with long duration of insulin treatment

We examined the responses of serum free C-peptide immunoreactivity (CPR) during a 100 g oral glucose tolerance test (OGTT) on diabetic patients undergoing different kinds and durations of treatment. None of the patients were ketosis-prone or had any history of nephropathy and they all developed diabetes when over the age of 30. The sigma serum free CPR (the sum of serum free CPR values during OGTT) of group A (duration of insulin treatment was less than 5 years, N = 10) was found to be higher than that of group B (duration of insulin treatment was 5 years or more, N = 10) (p less than 0.005). On the other hand, the sigma serum free CPR of group C (treatment with an oral hypoglycemic agent for less than 5 years, N = 9) was not statistically different from that of group D (treatment with an oral hypoglycemic agent for 5 years or more, N = 11). There were no statistical differences between group A and group B in age at onset, duration of diabetes, daily insulin dose, relative body weight index, serum creatinine or sigma BG (the sum of blood glucose values during OGTT). Just before the start of insulin treatment, there were no significant differences between the two groups in the following: 1. fasting blood glucose values (all 10 patients measured in group A and 9 patients in group B) 2. blood glucose and plasma immunoreactive insulin (IRI) responses (7 patients measured in group A and 6 in group B). Among those with plasma IRI measured on the previous occasion, sigma serum free CPR was found to be higher in group A than in group B (p less than 0.025) at the time of the present study.(ABSTRACT TRUNCATED AT 250 WORDS)     

Anomeric specificity in the response of gut glucagon-like immunoreactive materials to glucose.

An anomeric specificity of the glucose sensors of A cells and B cells of the pancreas has been reported. In this context the present authors investigated, using the canine intestinal loop prepared from the terminal portion of the ileum, how glucagon-like immunoreactive materials (GLI) of the gut would respond to glucose anomers in an attempt to explore a possible anomeric specificity of glucose-stimulated gut GLI secretion. As a result GLI was found to be more readily released into the blood stream after an intestinal alpha-glucose load than following beta-gluocse during a 15-minute observation period. It is thus suggested that gut GLI-secreting cells have glucose sensors similar to those of pancreatic A or B cells which are specific for the alpha-glucose anomer.     

Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes.     

Fulminant Type 1 diabetes in a pregnant woman as an initial manifestation of the insulin autoimmune syndrome

Diabet. Med. 29, 1335-1338 (2012) ABSTRACT: Fulminant Type 1 diabetes is a subtype of Type 1 diabetes characterized by (1) abrupt onset of diabetes, (2) very short duration of hyperglycaemia with mildly elevated HbA(1c) (相似文献   

Inhibition of pancreatic exocrine secretion and augmentation of the release of gut glucagon-like immunoreactive materials by intraileal administration of bile in the dog

The effect of intraileal instillation of bile, a stimulant of gut glucagon-like immunoreactive materials (gut GLI), on secretin-stimulated pancreatic secretion was examined in anesthetized dogs. Intraileal bile significantly inhibited the flow rate of secretin-stimulated pancreatic secretion. The inhibition of pancreatic secretion was accompanied by an elevation of plasma concentration of gut GLI. Taking the inhibitory effect of glucagon on pancreatic exocrine secretion into consideration, it could be reasonably postulated that gut GLI may be a mediator of bile-induced ileal inhibition of pancreatic exocrine function.     

Effects of exogenous growth hormone on insulin action and glucose metabolism in the dwarf 'little' mouse

The in vivo actions of growth hormone (GH) on insulin activity and glucose homeostasis were examined in the GH-deficient Little mouse. The insulin-like action of GH was revealed during glucose tolerance tests on the animals after acute treatment with the hormone and the insulin-antagonistic action was demonstrated in both glucose tolerance tests and insulin tolerance tests on the mice after chronic GH infusion. The primary mechanism of the GH actions is to influence the responses of the target tissues to circulating insulin in vivo. The pancreatic function seems to be of little importance in the alteration of glucose metabolism after acute exposure to GH as no significant change of the levels of plasma insulin was detected. It is concluded that the GH-deficient Little mouse is an ideal laboratory model for the elucidation of the molecular mechanism of the interaction between insulin and GH in the regulation of carbohydrate metabolism.     

Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP

Among the products of enteroendocrine cells are the incretins glucagon-like peptide-1 (GLP-1, secreted by L cells) and glucose-dependent insulinotropic peptide (GIP, secreted by K cells). These are key modulators of insulin secretion, glucose homeostasis, and gastric emptying. Because of the rapid early rise of GLP-1 in plasma after oral glucose, we wished to definitively establish the absence or presence of L cells, as well as the relative distribution of the incretin cell types in human duodenum. We confirmed the presence of proglucagon and pro-GIP genes, their products, and glucosensory molecules by tissue immunohistochemistry and RT-PCR of laser-captured, single duodenal cells. We also assayed plasma glucose, incretin, and insulin levels in subjects with normal glucose tolerance and type 2 diabetes for 120 min after they ingested 75 g of glucose. Subjects with normal glucose tolerance (n=14) had as many L cells (15+/-1), expressed per 1,000 gut epithelial cells, as K cells (13+/-1), with some containing both hormones (L/K cells, 5+/-1). In type 2 diabetes, the number of L and L/K cells was increased (26+/-2; P<0.001 and 9+/-1; P < 0.001, respectively). Both L and K cells contained glucokinase and glucose transporter-1, -2, and -3. Newly diagnosed type 2 diabetic subjects had increased plasma GLP-1 levels between 20 and 80 min, concurrently with rising plasma insulin levels. Significant coexpression of the main incretin peptides occurs in human duodenum. L and K cells are present in equal numbers. New onset type 2 diabetes is associated with a shift to the L phenotype.     

Changes in plasma inbulin related to the type of dietary carbohydrate in overweight hyperlipidemic male patients

Five patients with mild diabetes mellitus or angina pectoris were studied, each of whom consumed two sequential diets containing 40 to 50% carbohydrate. When 75% of the dietary carbohydrate was derived from food containing polysaccharides, the mean plasma insulin response to oral glucose was decreased relative to that seen following complementary diets providing carbohydrate mainly as simple sugars. Under both dietary conditions, glucose tolerance was improved compared to that seen prior to the study. These results suggest that with sugar restriction an improvement in the efficiency of the pancreatic beta-cell mechanism occurs. This effect may have been mediated by changes in the rate of secretion of pancreatic glucagon, or by an enteric secretogogue of insulin.     

Is GIP a glucagon cell constituent?

"Gastric inhibitory peptide" or "glucose-dependent insulin-releasing peptide" (GIP) is a member of the gut hormone family. Its physiological action is thought to be related to its insulinotrophic effect. The occurrence and distribution of GIP was studied by immunohistochemistry. In all species examined including man, GIP immunoreactivity was found to reside in the glucagon cells of the pancrease and gut. Three pancreatic glucagonomas were found to contain numerous cells displaying GIP and glucagon immunoreactivity. The GIP antiserum used did not cross react with either pancreatic-type or gut-type glucagon (GLI).