Standardization of IVGTT. Importance of method used to calculate glucose disappearance.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
N L Bodkin
Publications and source records attributed to N L Bodkin.
Central obesity in rhesus monkeys: association with hyperinsulinemia, insulin resistance and hypertriglyceridemia?
Total body fat and anthropometric assessments of fat distribution were examined in 23 lean and obese rhesus monkeys (Macaca mulatta). In addition, the relationships of central obesity to hyperinsulinemia, insulin resistance, glucose intolerance and hyperlipidemia were studied. Total body fat (as determined by the tritiated water dilution method), plasma glucose, insulin, lipoproteins (triglyceride, cholesterol and HDL- and LDL-cholesterol) and free fatty acids (FFA), and glucose disappearance rate (KG) and peripheral insulin-stimulated glucose uptake (M) were obtained. Results showed that abdominal circumference was the best predictor of body fat (r = 0.90; P < 0.001). There were strong linear relationships between abdominal circumference and plasma insulin (r = 0.66), glucose tolerance (r = -0.53), and M rate (r = -0.59) (all P < 0.05) but not to plasma glucose, lipoprotein fractions, or free fatty acids. When the subjects were grouped according to degree of obesity and insulin resistance (lean normals, obese insulin sensitive, and obese insulin resistant), the obese resistant monkeys had significantly higher plasma insulin levels, lower glucose tolerance, and significantly higher plasma triglyceride levels. We conclude that the spontaneously obese rhesus monkey is an excellent model of central obesity. Furthermore, in this model upper body obesity appears to be facilitative in the development of hyperinsulinemia, glucose intolerance and hypertriglyceridemia but does not appear to be causally related. In the rhesus monkey and in humans as well, we propose that the link between central obesity and these metabolic abnormalities may be peripheral insulin resistance.
Adipose Tissue↗
Correlation between plasma beta-cell tropin concentrations and body weight in obese rhesus monkeys.
The fasting plasma concentration of the pituitary peptide beta-cell tropin [beta-CT, adrenocorticotropic hormone-(22-39)] was measured in 17 rhesus monkeys from a colony known to develop spontaneous obesity. The weight of the animals was 9.4-23.9 kg (12-46% body fat). Plasma beta-CT concentrations were 0.03-0.84 nmol/l and were strongly correlated with body weight (P = 0.014, r = 0.584). Plasma beta-CT was also correlated with plasma insulin concentration as a power function (P = 0.011, r = 0.600) and with percent body fat up to 40% (P = 0.003, r = 0.0804). Plasma insulin is also correlated with body weight (P = 0.015, r = 0.578) but does not decline when body fat is in excess of 40%, supporting the hypothesis that beta-CT may be involved in a feed-back control mechanism, perhaps mediated by insulin. Because beta-CT has been shown in rodent studies to be a potent insulin secretagogue and lipogenic agent, it is possible that beta-CT is causally involved in the development of obesity and that there may be central determinants of obesity mediated through pituitary secretion of beta-CT.
Adipose Tissue↗
Insulin-like growth factor-I in non-insulin-dependent diabetic monkeys: basal plasma concentrations and metabolic effects of exogenously administered biosynthetic hormone.
Plasma insulin-like growth factor-I (IGF-I) concentrations and the effects of exogenous IGF-I administration were determined in 26 rhesus monkeys; each animal was well characterized regarding its degree of obesity, plasma glucose and insulin levels, and glucose tolerance (KG). Five separate groups were identified: lean normal, obese normoinsulinemic and normoglycemic, obese hyperinsulinemic with normal glucose tolerance, impaired glucose tolerant, and spontaneously diabetic (type II, non-insulin-dependent diabetes mellitus [NIDDM]). Basal plasma IGF-I levels in all monkeys ranged from 249 to 1,093 ng/mL and were strongly associated with age (r = -.66; P less than .001) and KG (r = .59; P less than .001), but not with body weight, body fat, or fasting plasma glucose or insulin levels. In addition, the acute insulin-like effects of exogenously administered IGF-I on glucose disappearance were studied in vivo in a dose-response comparison to insulin (subcutaneous administration of IGF-I at doses of 50, 100, or 200 micrograms/kg v insulin at 0.3 U/kg). Five hyperinsulinemic normoglycemic monkeys (fasting plasma glucose, 67 +/- 2 mg/dL; insulin, 163 +/- 42 microU/mL) and overt type II diabetic monkeys (fasting plasma glucose, 201 +/- 13 mg/dL; insulin, 38 +/- 6 microU/mL) each underwent a series of three to five experiments to determine the time course and degree of hypoglycemia induced by IGF-I as compared with insulin or with control (saline) injection.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Changes in lipoprotein concentrations during the development of noninsulin-dependent diabetes mellitus in obese rhesus monkeys (Macaca mulatta).
Abnormalities in plasma lipoprotein concentrations commonly found in subjects with noninsulin-dependent diabetes may be related to insulin resistance, hyperinsulinemia, hyperglycemia, or other metabolic defects. The middle-aged obese rhesus monkey is an animal model in which these defects can be separated in time during the development of diabetes. It is, therefore, a model system for examining the sequence of metabolic changes which occur before and after the onset of diabetes. This sequence of changes was used in the present study to determine if lipoprotein changes occur in association with the development of diabetes in the rhesus monkey. Increases in plasma triglyceride, very low density lipoprotein (VLDL) triglyceride, and VLDL cholesterol, and decreases in high density lipoprotein cholesterol were observed across previously identified groups ranging from normal to diabetic. Plasma triglycerides increased from 0.54 +/- 0.09 (normal) to 1.27 +/- 0.50, 1.93 +/- 0.79, and 4.28 +/- 2.24 in three intermediate groups with progressive hyperinsulinemia and insulin resistance, to 7.59 +/- 2.73 mmol/L in the diabetic monkeys. Increases in VLDL triglyceride and VLDL cholesterol paralleled the plasma triglyceride increases. High density lipoprotein cholesterol decreased across the groups from 2.33 +/- 0.16 (normal) to 1.72 +/- 0.20, 1.17 +/- 0.13, and 1.09 +/- 0.20 mmol/L in the intermediate groups, and was lowest in the diabetic monkeys, 1.00 +/- 0.21. The obese rhesus monkey can therefore be used to study lipoprotein abnormalities as they occur both before and in noninsulin-dependent diabetes.
Aging↗
Nutritional studies in nursing.
Explore the source record for details and available documents.
Appetite↗
Beta-cell hyperresponsiveness: earliest event in development of diabetes in monkeys.
Diabetes develops spontaneously in some, but not all, obese middle-aged monkeys. Longitudinal study of spontaneously obese rhesus monkeys has now shown the separation in time of the onset of various abnormalities associated with non-insulin-dependent diabetes mellitus (NIDDM). Glucose tolerance and acute and late insulin release were assessed at 6-mo to 1-yr intervals over a period of 7 yr in six young, lean, normal animals and 14 middle-aged obese, initially normoglycemic monkeys. Over 2-5 yr, while under study, five of the obese subjects developed overt diabetes [fasting plasma glucose greater than 140 mg/dl and decreased glucose disappearance rates (KG) less than 1.5]. Progressively increasing hyperinsulinemia leading to a 10-fold increase in basal plasma insulin levels (mean +/- SE = 443 +/- 69 microU/ml) and a fivefold increase in insulin response to glucose occurred independent of degree of obesity and before hyperglycemia. Later, basal and stimulated insulin levels declined before significant hyperglycemia. We conclude that in the monkey beta-cell function is clearly enhanced, not reduced, in the earliest stages of the progression to NIDDM but is reduced just before overt diabetes.
Aging↗
A comparative study of zopiclone and triazolam in patients with insomnia.
Zopiclone, a cyclopyrrolone derivative, was compared with triazolam in a double-blind, randomized, parallel group study in general practice patients suffering from insomnia. Both drugs were found to be effective compared to baseline assessment in that they increased the number of hours of sleep, reduced the number of nocturnal wakenings and reduced the latency of falling asleep. In addition, both drugs improved patients' condition following awakening, with zopiclone showing slight superiority. In both treatment groups, there was a transient period of poor sleep after withdrawal of the drug, and one patient in each group withdrew from the study for this reason. There were no serious adverse reactions during the trial.
Adult↗
Hepatic glucose production and insulin sensitivity preceding diabetes in monkeys.
The purpose of this study was to identify the relationship between basal hepatic glucose production (HGP) and peripheral insulin sensitivity as assessed by the hyperinsulinemic euglycemic clamp prior to and during the development of non-insulin-dependent (type 2) diabetes mellitus in rhesus monkeys. Twenty-six male monkeys (Macaca mulatta), including normal animals and monkeys in various phases of the development of spontaneous obesity-associated type 2 diabetes were studied. Fasting plasma glucose (FPG) and insulin (FIRI), basal HGP using a [3H]glucose infusion, and peripheral insulin sensitivity (as determined by the euglycemic clamp technique) were examined. The earliest change that could be detected was a significant reduction in peripheral insulin sensitivity accompanied by increased FIRI. These changes preceded a significant deterioration of glucose tolerance. Basal HGP changed in parallel with FPG (r = 0.90, P less than 0.001), becoming significantly elevated only when FPG rose to levels diagnostic of diabetes (greater than 140 mg/dl). Thus basal HGP and fasting glucose levels showed no significant changes early in the development of type 2 diabetes. We conclude that the early serial decreases in insulin sensitivity and progressive increases in FIRI, with or without decreased glucose tolerance, are prognostic of the future development of diabetes in obese monkeys, a longitudinal process that is also likely to be observed in most if not all obese humans progressing to diabetes.
Animals↗
Heterogeneity of insulin responses: phases leading to type 2 (non-insulin-dependent) diabetes mellitus in the rhesus monkey.
To determine the natural history of the development of Type 2 (non-insulin-dependent) diabetes mellitus, basal plasma insulin and glucose levels and responses to intravenous glucose tolerance tests were determined over a period of 6 years in 42 adult male rhesus monkeys (Macaca mulatta). Among the 28 obese monkeys (percent body fat greater than 22%) over the age of 10 years, 9 developed overt Type 2 diabetes (fasting plasma glucose, greater than 7.8 mmol/l, and reduced glucose disappearance rates, KG less than 1.5), and 14 monkeys have shown progressive changes which suggest that they may also become diabetic. Application of a highly constant antecedent diet and a consistent 16-h fast minimized experimental variability, and permitted the identification of 8 phases in the progression from normal lean young adult to overt Type 2 diabetes. The earliest changes which could be detected were a slight increase followed by a progressive rise in fasting plasma insulin levels and an increased insulin secretion in response to a glucose stimulus. These events preceded by several years the onset of a gradual deterioration of glucose tolerance. We found that hyper-, normo-, or hypoinsulinaemia could be associated with normoglycaemia or varying degrees of hyperglycaemia; however, the prospective longitudinal study of individual monkeys clearly identified this apparent heterogeneity of plasma insulin and glucose levels as reflecting sequential changes in a continuum of events preceding or accompanying the development of impaired glucose tolerance and Type 2 diabetes mellitus.
Animals↗
Nutrient composition: effects on appetite in monkeys with oral factors held constant.
The effects of macronutrients on appetite and total caloric intake in monkeys (Macaca mulatta) was studied using a new feeding and infusion system which yoked intragastric infusion of various nutrients to oral ad lib intake and removed the confounding factor of palatability from the assessment of nutrient effects on feeding behavior. A suction-activated liquid diet feeding system provided free access to a nutritionally complete diet, with 1 ml of diet delivered orally by pump with each discrete suck by the monkey. A second pump was yoked to the oral feeding pump and delivered various nutrients directly into the stomach via an implanted intragastric cannula. Thus, while oral diet composition remained constant, the net diet reaching the stomach varied over ranges of 28 to 77% carbohydrate, 16 to 65% fat and 7 to 36% protein. No significant differences in total caloric intake were observed between intakes of diets with net composition of high carbohydrate or high fat. When protein was increased to 36%, total caloric intake was generally reduced, and this effect was sustained for at least 3 weeks. Therefore, protein appears to have an increased specific satiating effect beyond the caloric content, when compared to carbohydrate or fat.
Animals↗