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Biomedical subjects

B C Hansen

Publications and source records attributed to B C Hansen.

At least 73 records · Page 4Linked to original sources
PubMed1993

Primary prevention of diabetes mellitus by prevention of obesity in monkeys.

Many, but not all, adult rhesus monkeys spontaneously develop significant increases in body fat mass, and many, but not all, progress to develop overt adult-onset type II diabetes. The purpose of this study was to determine whether both an increase in body fat and onset of diabetes could be simultaneously prevented through long-term maintenance of stable normal adult body weight by caloric titration. Eight adult male monkeys were provided a complete normal chow diet, but with daily amounts restricted and titrated on a weekly basis to maintain a constant body weight (weight-stabilized group). This regimen has been continued for 5-9 yr (mean +/- SD of 7 +/- 0.5 yr) with monkeys attaining the age of 17.9 +/- 0.6 yr and with maintenance of normal body fat (17.7 +/- 1.8%). The age-matched ad libitum fed group (18.1 +/- 0.2 yr of age) consisted of 19 monkeys maintained under identical laboratory conditions and diet, but with food available ad libitum. Results showed weight-stabilized monkeys weighed significantly less than ad libitum fed monkeys (10.4 +/- 0.2 vs. 16.1 +/- 0.7 kg, respectively, P < 0.05) and had significantly better glucose tolerance as measured by Kglucose (glucose disappearance rate) (3.9 +/- 0.3 vs. 2.4 +/- 0.2, P +/- 0.05). Of the 19 ad libitum fed age-matched monkeys, 4 were overtly diabetic, and 6 others had significantly reduced glucose tolerance. Hyperinsulinemia did not develop in the weight-stabilized group, and beta-cell response to glucose remained normal; both were significantly different from the exaggerated levels of the ad libitum fed group (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1993

Effects of dietary protein concentration (corn:soybean meal ratio) and body weight on nitrogen balance of growing boars, barrows, and gilts: mathematical descriptions.

The effects of dietary CP level (actually corn:soybean meal ratio) and BW on N intake, N digestibility, the efficiency of utilization of N (apparent biological value), and N retention were measured in 36 pigs: 12 boars (five collection periods), 12 barrows (four collection periods), and 12 gilts (nine collection periods). Initial and final BW of the boars, barrows, and gilts were 19, 24, and 27 kg and 80, 69, and 110 kg, respectively. Diets were based on corn and soybean meal and contained 11 to 23% CP. Averaged over all collection periods, N retention was 24.2, 20.0, and 19.8 g/d for boars, barrows, and gilts, respectively. The response of N retention to CP levels was quadratic (P < .15) and cubic (P < .01) for boars, linear (P < .01) and quadratic (P < .05) for barrows, and linear (P < .15) for gilts. Rates of N retention responded quadratically (P < .001) for all sexes as pigs gained weight, reaching a maximum when pigs weighed 55 to 65 kg. Multiple-regression analyses were conducted and equations were developed that described the effects of CP level (or lysine intake) and BW on N retention for each sex. The results indicated that N balance was a function of both CP level (or lysine intake) and BW and that the nature of the response differed for each sex.

Analysis of Variance↗
PubMed1993

Effects of dietary protein concentration (corn:soybean meal ratio) on the performance and carcass characteristics of growing boars, barrows, and gilts: mathematical descriptions.

Three split-plot trials using completely randomized whole-plot designs were conducted to determine the effect of dietary CP level (corn: soybean meal ratio) on daily feed intake, rate and efficiency of gain, and carcass characteristics of growing boars, barrows, and gilts. One hundred eighty-nine pigs were assigned to seven corn-soybean meal diets ranging from 11 to 23% CP in two-percentage-unit increments. The pigs were penned individually and had ad libitum access to feed and water. The average initial weight was 19 kg and the average final weight was 105 kg. Regression analysis revealed that maximal rates and efficiencies of gain were attained by all sexes when animals consumed diets that contained 17 to 19% CP. Average daily gain increased linearly as dietary lysine intake increased from 5 g/d to approximately 25 g/d. Carcass leanness increased at a greater rate for boars than for barrows and gilts (P < .05) as CP levels increased from 11 to 19% CP. The results indicated that both inadequate and excess dietary CP concentrations are detrimental to the rate and efficiency of gain and carcass quality of growing-finishing boars, barrows, and gilts. Interactions between sex and CP level indicated that inadequate CP concentrations were more detrimental to boars than to barrows and gilts.

Adipose Tissue↗
PubMed1993

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↗
PubMed1992

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

Low urinary chiro-inositol excretion in non-insulin-dependent diabetes mellitus.

BACKGROUND AND METHODS: Inositol is a major component of the intracellular mediators of insulin action. To investigate the possible role of altered inositol metabolism in non-insulin-dependent diabetes mellitus (NIDDM), we used gas chromatography and mass spectrometry to measure the myo-inositol and chiro-inositol content of urine specimens from normal subjects and patients with NIDDM: The study subjects were whites, blacks, and Pima Indians. The type of inositol and its concentration in insulin-mediator preparations from muscle-biopsy specimens from normal subjects and diabetic patients were also determined. RESULTS: The urinary excretion of chiro-inositol was much lower in the patients with NIDDM (mean [+/- SE], 1.8 +/- 0.8 mumol per day) than in the normal subjects (mean, 84.9 +/- 26.9 mumol per day; P less than 0.01). In contrast, the mean urinary myo-inositol excretion was higher in the diabetic patients than in the normal subjects (444 +/- 135 vs. 176 +/- 46 mumol per day; P less than 0.05). There was no correlation between chiro-inositol excretion and the age, sex, or weight of the diabetic patients, nor was there any correlation between urinary chiro-inositol and myo-inositol excretion in either group. The results were similar in a primate model of NIDDM, and chiro-inositol excretion was decreased to a lesser extent in animals with prediabetic insulin resistance. chiro-Inositol was undetectable in insulin-mediator preparations from muscle-biopsy samples obtained from patients with NIDDM: Similar preparations from normal subjects contained substantial amounts of chiro-inositol. Furthermore, the chiro-inositol content of such preparations increased after the administration of insulin during euglycemic-hyperinsulinemic-clamp studies in normal subjects but not in patients with NIDDM: CONCLUSIONS: NIDDM is associated with decreased chiro-inositol excretion and decreased chiro-inositol content in muscle. These abnormalities seem to reflect the presence of insulin resistance in NIDDM:

Age Factors↗
PubMed1990

Food intake and meal patterns in rhesus monkeys: significance of chronic hyperinsulinemia.

To investigate the role of plasma insulin on food intake, we have examined the effect of naturally occurring chronic hyperinsulinemia on the feeding behavior of male rhesus monkeys. Two groups of monkeys, a group with normal fasting insulin concentrations (52.4 +/- 2.2 microU/ml) (mean +/- SE) and a hyperinsulinemic group (148.6 +/- 14.5 microU/ml), were selected to be similar in weight, 13.0 +/- 1.0 and 15.3 +/- 0.5 kg, respectively, prior to study. Food intake and feeding patterns were recorded and analyzed. No differences in either daily caloric intake, 815.2 +/- 27.4 versus 890.0 +/- 64.2 kcal (p less than 0.32), or feeding patterns were found. The number of meals taken per day did not differ between the two groups, 8.7 +/- 1.7 versus 6.7 +/- 1.1 (p less than 0.35), nor did meal size differ, 129 +/- 16.5 versus 110.5 +/- 16.3 (p less than 0.45). We conclude that chronic endogenous hyperinsulinemia as it occurs naturally in some obese rhesus monkeys has no significant effect on daily feeding behavior.

Animals↗
PubMed1990

Postingestional effects of a high-protein diet on the regulation of food intake in monkeys.

Using a system in which the composition of an intragastric diet could be manipulated while oral factors were kept constant, we studied the effect of a high-protein diet on food intake. Four adult rhesus monkeys with chronically implanted intragastric cannulas were trained to use suction-activated food pumps that were monitored by computer so feeding pattern could be assessed over periods averaging 4 wk each. Each suck delivered the oral control diet while simultaneously activating a second pump, which delivered a second diet directly into the stomach, resulting in net diet compositions of either 14% or 50% protein. The calorie intake was consistently reduced by 24.7 +/- 1.6% when the high-protein diet was fed. The effect on intake was not due to increased diet osmolality. A doubling in plasma branched-chain amino acid concentration occurred when the high-protein diet was fed. These data indicate that feeding a high-protein diet results in a physiological appetite suppression, possibly mediated through branched-chain amino acids.

Amino Acids↗
PubMed1990

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↗
PubMed1989

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↗