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Biomedical subjects

D J Chisholm

Publications and source records attributed to D J Chisholm.

At least 109 records · Page 6Linked to original sources
PubMed1983

Comparison of potency of porcine insulin and semisynthetic human insulin at 3 dose levels using the euglycaemic clamp.

The relative potency of porcine insulin and semisynthetic human insulin has been examined in humans using the euglycaemic glucose clamp technique. Three 90 minute consecutive infusions at 2.4, 4.8 and 7.2 units/hr were administered to 7 normal subjects. The rate of glucose infusion (mg/min, mean +/- SEM) required to maintain euglycaemia during the last 40 minutes of each insulin infusion for porcine (P) and human (H) insulin was not significantly different. However, when the glucose infusion rate was expressed as a function of the mean serum insulin level (mU/l) over the same period of time the values for P and H at 4.8 and 7.2 U/hr were not significantly different but H was greater than P (13.6 +/- 1.9, v 10.8 +/- 1.9, p less than .05) at 2.4 U/hr. Mean serum insulin levels did not differ significantly for human or porcine insulin infusion. This study confirms the similarity in potency between human and porcine insulin in the human. However, delivery at 2.4 U/hr, which would predominantly affect hepatic glucose output, suggests that semisynthetic human insulin is more potent than porcine insulin with respect to the liver.

Adult↗
PubMed1983

Influence of obesity on basal glucagon levels in non-diabetic and diabetic Nauruans.

Basal plasma glucagon (IRG), insulin (IRI) and glucose levels were measured in normal weight (Body Mass Index (BMI) less than 30) and obese (BMI greater than or equal to 30) non-diabetic and diabetic Micronesians (n = 30) on Nauru Island. This population has a high prevalence of diabetes mellitus. IRG levels were significantly higher (P less than 0.02) in the non-diabetic obese, compared to the non-diabetic lean subjects (109 +/- 19 vs 44 +/- 12 SEM pg/ml, respectively) and there was a significant positive correlation between basal IRG and BMI (r = 0.79, P less than 0.001). IRG levels were similar in diabetic obese and diabetic lean subjects. The pathophysiological significance of the hyperglucagonaemia in these obese subjects is not known, although it may be related to the frequent development of diabetes in this unique population.

Adult↗
PubMed1983

In vivo insulin sensitivity in the rat determined by euglycemic clamp.

Our aim was to develop the glucose clamp (GC) technique in the conscious rat for assessment of in vivo insulin sensitivity. A 2-h euglycemic GC could be performed in chronically cannulated rats using 625 microliter blood. Overnight-fasted rats were infused with porcine insulin (1.67 mU . kg-1 . h-1). Insulin levels of 41 +/- 2 (SE) mU/liter were produced in rats aged 91 +/- 4 days with a 60- to 120-min glucose infusion rate (GIR60-120) of 10.6 +/- 0.6 mg . kg-1 . min-1 (n = 9) during euglycemia. GIR60-120 was significantly (P less than 0.025) reduced in rats aged greater than 130 days (mean, 169 +/- 16 days) to 7.7 +/- 1.2 mg . kg-1 . min-1 (n = 7). Metabolic clearance rate of porcine insulin (46 +/- 3 ml . kg-1 . min-1) and GIR60-120 compared with plateau plasma insulin levels are higher than values reported in humans. The latter may be due to suppression of a higher basal hepatic glucose production or increased potency of porcine compared with native insulin. We conclude that the GC can be accomplished in the rat. When combined with tracer administration and subsequent killing, it should provide a quantitative in vivo measurement of insulin sensitivity in individual tissues.

Animals↗
PubMed1983

Effect of acute exercise and prolonged training on insulin response to intravenous glucose in vivo in rat.

Physical training causes hypoinsulinemia and enhanced insulin sensitivity. Insulin sensitivity is also enhanced by a single bout of exercise. However, changes in beta-cell responsiveness with acute exercise are ill defined. To clarify these relationships intravenous glucose tolerance tests were performed in 1) physically trained rats (3 different levels), 48 h after the last bout of exercise; 2) untrained rats, 0.5, 4, and 24 h after a single bout of exercise; or 3) sedentary control rats. The total area under the glucose-stimulated insulin response curve (GSIR) was negatively correlated with total distance run during training (r = -0.45, P less than 0.05), whereas glucose tolerance was improved (P less than 0.005 vs. controls) with intensive training. GSIR was suppressed by 38% (P less than 0.01 vs. controls) 0.5 h after a single bout of exercise. This effect persisted for 4 h but was not present after 24 h. These results indicate that a single bout of exercise induces suppression of GSIR which lasts less than 24 h. In contrast, physical training induces prolonged suppression (for at least 48 h) of GSIR, proportional to the intensity of training, and improved glucose tolerance.

Animals↗
PubMed1982

An evaluation of dynamic pituitary function tests in patients with pituitary tumours.

In a prospective study of 26 patients with macroadenoma of the pituitary (14 secretory and 12 non-secretory), basal and stimulated pituitary hormone levels were used to detect hypothalamic dysfunction and to examine pituitary hormone secretion before and after hypophysectomy. Suprasellar tumour extention with hypothalamic compression occurred in 18 patients but was not consistently associated with hormonal tests indicative of hypothalamic dysfunction. In patients with secretory tumours, secretory activity was adequately assessed by basal hormone levels alone, which showed that surgery reduced hormone levels by a mean 85% in acromegaly and by a mean 55% in prolactinomas. Preoperatively, pituitary reserve of hormones not being hypersecreted was often normal, despite large tumour size and hypothalamic compression. Even after apparently complete pituitary removal at surgery, normal responses to stimulatory tests could sometimes be detected. Conventional dynamic tests are only of limited value in the assessment of hypothalamo-pituitary dysfunction in patients with large pituitary tumours and should not be used indiscriminately in such individuals requiring surgery.

Acromegaly↗
PubMed1981

Insulin precipitation in artificial infusion devices.

Precipitation of insulin is a problem with mechanical insulin infusion devices. Therefore conditions affecting insulin precipitation have been studied in a recirculating system using a peristaltic pump. Acetate buffer favoured precipitation and a pH of 2, 3 or 8 resulted in no less (and often more) precipitation than a pH of 7 using either acetate of phosphate buffer. However, no precipitation occurred in a phosphate buffered neutral preparation after ten days of pumping through tubing pretreated with EDTA. In comparison at pH 7, using acetate buffer with untreated tubing, more than 95% of insulin was precipitated in ten days. A heavy metal-insulin association appears to be a major factor in the precipitation. However, some formation of insulin fibrils is probable as the precipitate is autocatalytic and partially acid insoluble. Phosphate buffered highly purified porcine insulin is suitable for relatively prolonged infusion if metal ion contamination of the delivery system is minimised.

Buffers↗
PubMed1981

Timing of insulin delivery with meals.

In non-diabetics neural and/or gastrointestinal humoral factors cause anticipatory insulin release with meals. The importance of this mechanism was illustrated by administration of a standard meal to six insulin dependent diabetics on two occasions. Insulin was delivered intravenously by an "open-loop" (preprogrammed) insulin infusion system designed to simulate the normal insulin response to meals. On one occasion insulin delivery was delayed 15 minutes. This time approximates the physiology delay before blood glucose rises after the start of a meal. The delay resulted in significantly greater hyperglycaemia continuing over three hours, compared with the study in which insulin delivery increased coincident with the start of the meal. A mechanism for initiating early insulin release with meals would be a helpful addition to "closed-loop" insulin delivery systems, this being apparent in a further comparison made between performance of the open-loop and closed-loop systems. Moreover, the delayed insulin response seen in maturity onset diabetics is likely to be an important cause of persistent hyperglycaemia.

Blood Glucose↗
PubMed1979

Glucagon metabolism in normal subjects and in cirrhotic patients before and after portasystemic venous shunt surgery.

The effect of portasystemic shunt surgery on basal immunoreactive glucagon (IRG) levels, metabolic clearance rate (MCR) and t 1/2 for glucagon decay, and basal systemic delivery rate (BSDR) of glucagon was investigated in paired studies in ten cirrhotic subjects. The degree of hepatocellular dysfunction and extent of portasystemic venous shunting was also recorded. Basal IRG levels were highest in the post-shunt (mean +/- SEM, 382 +/- 73 pg/ml) as compared to the pre-shunt (213 +/- 27 pg/ml; P less than 0.05) cirrhotic and control (53 +/- 13 pg/ml; P less than 0.005) groups. The MCR of glucagon was similar in control (13.0 +/- 1.3 ml/kg/min) and pre-shunt cirrhotic patients (13.3 +/- 1.7 ml/kg/min) but was significantly (P less than 0.02) decreased in the post-shunt cirrhotics (7.6 +/- 1.3 ml/kg/min). The t 1/2 for glucagon decay was similar in the control and cirrhotic groups. The BSDR, an estimate of pancreatic A cell secretion, was increased four-fold (P less than 0.01) in the pre-shunt (3042 +/- 454 pg/kg/min) and post-shunt (2518 +/- 535 pg/kg/min) cirrhotic groups, as compared to controls (750 +/- 244 pg/kg/min). It is concluded that (a) in the presence of cirrhosis, the magnitude of portasystemic shunting is important in determining the degree of hyperglucagonaemia; (b) in preshunt cirrhotics raised basal IRG levels are principally due to A cell hypersecretion of glucagon whereas in post-shunt cirrhotics riased IRG levels reflect both A cell hypersecretion and delayed clearance of glucagon; and (c) acute shunting of splanchnic venous blood away from the liver reduces the clearance of glucagon, suggesting that, in man, the liver contributes to the clearance of circulating glucagon.

Adult↗
PubMed1979

Effect of portasystemic venous shunt surgery on hyperglucagonaemia in cirrhosis: paired studies of pre- and post-shunted subjects.

The effect of liver disease on glucagon metabolism was examined in nine patients with chronic liver disease who were studied both before and after the creation of a surgical portasystemic shunt. Hepatocellular function did not deteriorate after shunt surgery. However, hepatic perfusion with splanchnic venous blood, as determined by scintisplenoportography, decreased after shunt surgery in six subjects but appeared unaltered in three. Basal plasma immunoreactive glucagon (IRG) levels in the pre-shunt cirrhotic group were significantly greater (p <0.005) than in control subjects and further increased (p <0.05) after shunt surgery. Moreover, the increase in basal IRG after shunt was evident only in patients in whom portasystemic shunting was demonstrably increased by surgery. Despite the higher basal IRG levels postoperatively, shunt surgery in the cirrhotics did not alter basal glucose and insulin levels or the glucose and insulin response to a glucose or protein load. Circulating IRG was heterogeneous in the pre-shunt cirrhotic patients: the 9000 molecular weight fraction comprised 27+/-4%, the 3500 mol. wt. fraction 71+/-4%, and the > 40 000 mol. wt. fraction was minimal. After shunt surgery, the relative proportion of the 9000 mol. wt. fraction of IRG (13+/-3%) decreased significantly (p <0.05) and this fall was associated with a corresponding increase in the 3,500 mol. wt. fraction (84+/-4%). It is concluded that, in cirrhosis, hyperglucagonaemia is: (1) dependent on the degree of portasystemic shunting rather than impaired hepatocellular function; (2) predominantly due to increased circulating 3500 molecular weight glucagon; and (3) not a major factor in the pathogenesis of carbohydrate intolerance in liver disease.

Adult↗
PubMed1979

Hyperglycemia and glucagon suppression: possible importance of the vagus and enteric humoral factors.

Augmentation of insulin release after oral glucose by a gastrointestinal humoral mechanism is well accepted. The suggestion of a similar mechanism for suppression of glucagon release after oral glucose has not been previously tested. In this study, plasma glucagon levels have been estimated in five normal subjects after both oral and iv administration of glucose. A variable iv glucose infusion rate with frequent monitoring of blood glucose was used to match the hyperglycemia produced by the 50 g oral glucose and the iv glucose loads. Virtually complete suppression of plasma glucagon levels was seen in both cases (nadir of glucagon levels 16 +/- 6 pg/ml for oral glucose; 11.4 +/- 3 pg/ml for iv glucose). Thus, enteric humoral factors did not facilitate glucagon suppression after oral glucose ingestion in man. The vagus nerve is also involved in mediating the alpha-cell response to hypoglycemia and, thus, to examine whether hyperglycemia suppresses glucagon release through a vagal mechanism, iv atropine (15 microgram/kg) was given 20 min before administration of oral or iv glucose. Atropinization delayed the glucagon suppression after oral glucose, but this delay was probably related to delayed glucose absorption from the gut. With iv glucose, atropinization did not affect the degree of suppression of glucagon levels. It is concluded that alpha-cell suppression in response to hyperglycemia is not mediated via the vagus.

Adult↗
PubMed1978

Insulinoma: poor recognition of clinical features is the major problem in diagnosis.

Traditionally it is taught that hypoglycaemia may cause a clinical picture which mimics a variety of neurological and psychiatric disorders. Yet patients with insulinoma continue to baffle many medical specialists, who presumably are not sufficiently aware of the clinical features of hypoglycaemia. After examining medical records of seventeen patients, diagnosed as suffering from "insulinoma" in major Melbourne hospitals from 1971 to 1976, it was evident that these patients frequently undergo extensive investigations for supposed neurological disorders, the correct diagnosis being missed until they develop catastrophic symptoms. Of these seventeen patients, the diagnosis was made with reasonable speed in only six cases, while eight patients were initially discharged from hospital with a completely erroneous diagnosis. It seems likely that a number of patients with insulinoma, whose symptoms are less dramatic than those reported here, are being mistakenly treated as having epileptiform or psychiatric disorders.

Adenoma, Islet Cell↗
PubMed1977

Ketoacidosis in pancreatectomized man.

We investigated the importance of glucagon in the development of diabetic ketoacidosis by withholding insulin from six patients with juvenile-type diabetes and four totally pancreatectomized subjects. Patients were fasting and had previously been maintained on intravenous insulin for 24 hours. In diabetic patients plasma glucagon concentrations rose sharply after withdrawal of insulin, and the increases were accompanied by a rise in blood ketone concentration of 4.1+/-0.7 (S.E.M.) and blood glucose concentration of 12.5+/-1.8 mmol per liter by 12 hours. In the pancreatectomized patients, despite the absence of measurable glucagon, blood ketones rose by 1.8+/-0.8 and blood glucose by 7.7+/-1.5 mmol per liter. Thus, glucagon is not essential for the development of ketoacidosis in diabetes, as has previously been suggested, but it may accelerate the onset of ketonemia and hyperglycemia in situations of insulin deficiency.

Acetoacetates↗