Biomedical subjects

S M Hampton

Publications and source records attributed to S M Hampton.

42 records · Page 3Linked to original sources

PubMed1987

Immunoreactive C-peptide in spontaneous syndromes of obesity and diabetes in mice.

Immunoreactive C-peptide was evaluated in the plasma and pancreas of Aston ob/ob and C57BL/KsJ db/db mice in relation to disturbances in pancreatic B-cell function. At 18-24 weeks of age, ob/ob and db/db mice displayed hyperglycaemia (1.6 and 3.8 fold increases respectively) and hyperinsulinaemia (10.8 and 5.1 fold increases respectively) despite a similar pancreatic insulin content to their respective non-diabetic lean control mice. Immunoreactive C-peptide concentrations in the plasma and pancreas of the mutants corresponded with the degree of hyperinsulinaemia and pancreatic insulin content, and the insulin: C-peptide molar ratios in both mutants were similar to lean controls. In ob/ob mice parenteral glucose administration decreased plasma insulin and C-peptide concentrations, despite markedly raised glucose concentrations. However, administration of a low dose of insulin (5 U/kg) to lean mice and much higher doses of insulin (50 and 120 U/kg) to ob/ob mice markedly decreased plasma glucose and C-peptide concentrations. When the rate and extent of insulin-induced glucose suppression observed in ob/ob mice was mimicked in lean mice, an almost complete (95%) inhibition of C-peptide was achieved compared with a 57% decrease in the ob/ob mutant. Injection of ob/ob mice with glucose to counter the insulin-induced hypoglycaemia failed to affect the fall of C-peptide concentrations. The data suggest that the metabolic processing of insulin and C-peptide are undisturbed in obese-diabetic mice, and that the impaired suppression of circulating C-peptide by insulin-hypoglycaemia in ob/ob mice predominantly reflects impaired feedback inhibition by insulin.

Animals↗

PubMed1986

Specific binding of the C-peptide of proinsulin to cultured B-cells from a transplantable rat islet cell tumor.

Specific binding of the C-peptide of proinsulin was evaluated using a transplantable NEDH rat islet cell tumour predominantly composed of insulin-secreting B-cells. Cultured tumour B-cells exhibited greater than 90% viability assessed by trypan blue exclusion, and retained the ability to form tumours with accompanying hypoglycaemia and hyperinsulinaemia after reimplantation. During binding experiments with synthetic rat C-peptide I and iodinated tyrosylated rat C-peptide I, tumour B-cells exhibited 54 +/- 6% specific binding. Displacement of tracer increased with increasing concentrations of unlabelled rat C-peptide I (0.25-1,000 ng/ml), and the specificity of binding was substantiated by reduced displacement with human C-peptide. Scatchard analysis of specific C-peptide binding revealed a curvilinear plot with upward concavity. The demonstration of specific C-peptide binding to insulin-secreting B-cells provides evidence for a physiological role of proinsulin C-peptide.

Adenoma, Islet Cell↗

PubMed1986

Insulin and C-peptide levels after oral and intravenous glucose. Contribution of enteroinsular axis to insulin secretion.

Peripheral venous plasma insulin and C-peptide concentrations were measured in 10 healthy volunteers, given either 100 g glucose orally or sufficient intravenous (i.v.) glucose to produce similar glucose concentrations when measured in arterialized blood. The incremental areas under both the insulin and C-peptide curves were significantly increased after oral as compared with i.v. glucose administration by 229% and 138%, respectively. Arteriovenous plasma glucose differences were higher after oral glucose administration and were positively correlated with plasma insulin concentrations. Plasma gastric inhibitory polypeptide (GIP) and insulin concentrations were measured in seven healthy volunteers given oral glucose loads ranging from 25 to 200 g. Both the magnitude and duration of the GIP and insulin responses after oral glucose ingestion were dose dependent. These results suggest that the main cause of the increase in peripheral insulin levels after large oral carbohydrate loads is augmented insulin secretion rather than reduced hepatic extraction, indicating the possibility that an enteroinsular factor does exist, in accordance with the "incretin" concept. They also emphasize the need to document both arterial and venous glucose concentrations for the correct interpretation of experiments investigating glucose homeostasis.

Administration, Oral↗

PubMed1983

Effect of pretreatment with a high fat diet on the gastric inhibitory polypeptide and insulin responses to oral triolein and glucose in rats.

Male Wistar rats were pretreated with 3 ml triolein orally for 4 days in addition to their normal diet. A similar control group were allowed free access to normal laboratory food. When given an oral fat load (1 ml triolein) plasma gastric inhibitory polypeptide (GIP) and triglyceride levels were significantly higher in the fat pretreated group. Inhibition of fat-stimulated GIP release by exogenous insulin was demonstrated in the untreated control group (plasma GIP: 663 +/- 49 versus 853 +/- 92 ng/l, mean +/- SEM p less than 0.025), but pretreatment with an oral fat load abolished this effect (plasma GIP: 1008 +/- 95 versus 1116 +/- 100 ng/l, p NS). Plasma glucose levels were significantly higher in fat pretreated rats given oral fat and intraperitoneal insulin compared with untreated controls (plasma glucose nadir 2.6 +/- 0.48 versus 1.6 +/- 0.15 mmol/l, p less than 0.05). Fat-pretreated rats showed significantly higher insulin and glucose levels compared with the untreated rats when given oral glucose (plasma insulin: 6.2 +/- 1.2 versus 2.5 +/- 0.59 micrograms/l, p less than 0.01; plasma glucose: 10.2 +/- 0.39 versus 8.9 +/- 0.41 mmol/l, p less than 0.025). Pretreatment of rats on a high fat diet causes (1) increased GIP secretion in response to an oral fat load, (2) abolition of the feed-back inhibition of exogenous insulin on fat-stimulated GIP release, and (3) some degree of insulin resistance.

Animals↗

PubMed1980

Endocrine pancreatic control of the release of gastric inhibitory polypeptide. A possible physiological role for C-peptide.

Intravenous infusion in anaesthetized rats of rat II C-peptide at a dose which produced circulating levels of 22.8 +/- 1.8 nmol/l after 30 min, resulted in a significant reduction (141 +/- 7 to 50 +/- 4 pmol/l, p < 0.001, mean +/- SEM) in the immunoreactive gastric inhibitory polypeptide response to an intestinal perfusion with a fat emulsion. Immunoreactive insulin levels were unchanged from basal in this study. It is suggested that C-peptide must be considered as a candidate for the endocrine pancreatic factor which exerts a negative feedback upon gastric inhibitory polypeptide release.

Animals↗

PubMedDate not supplied

Monitoring beta cell responses in obese and normal weight subjects--a pilot study.

Six obese and six normal subjects were given a test meal after an overnight fast. Blood glucose, plasma immunoreactive C peptide, immunoreactive insulin and proinsulin plus its circulating fragment des Lys64, Arg65 proinsulin were measured. Responses to the test meal were not significantly different for immunoreactive C peptide and insulin concentrations. Plasma insulin responses were similar in the two groups. Plasma C-peptide values showed wide variations in the obese subjects. Plasma proinsulin and proinsulin fragment levels rose slightly in the normal subjects reaching a peak level of 28.9 +/- 6.4 pmol/l whereas in the obese subjects these same levels rose to a maximum of 88 +/- 45 pmol/l. However because of the large intra group variation, differences were not significant.

Adult↗