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D Porte

Publications and source records attributed to D Porte.

At least 91 records · Page 5Linked to original sources
PubMed1988

Insulin resistance and beta-cell dysfunction in aging: the importance of dietary carbohydrate.

Aging is associated with a progressive decrease in glucose tolerance. This decrease is associated with insulin resistance and beta-cell dysfunction. This study was performed to evaluate the possible role of dietary factors in the glucose intolerance of aging. Two groups of men were studied: one young (Y; n = 8; age range, 18-36 yr) and one elderly (E; n = 10; age range, 65-82 yr). Frequently sampled iv glucose tolerance tests were performed in random order: 1) during ad libitum home dietary conditions; 2) after a 3- to 5-day regimen of very high (85%) carbohydrate intake; and 3) after a 3- to 5-day regimen of low (30%) carbohydrate intake (Y only). From the frequently sampled iv glucose tolerance test data, we calculated the glucose disappearance rate (Kg) and metabolic parameters according to the minimal model method, including the insulin sensitivity index (S1) and the first and second phase beta-cell responsivity to glucose (phi 1 and phi 2). The elderly men, while eating an ad libitum diet, were less tolerant to glucose than the young [mean Kg: E = 1.5 +/- 0.2% (+/- SE) min-1; Y = 2.3 +/- 0.3% min-1; P less than 0.025], had relative insulin resistance (mean Si: Y = 6.1 +/- 1.1; E = 2.4 +/- 0.7 min-1 10(-4)/(microU/mL) [0.85 +/- 0.15 vs. 0.33 +/- 0.10 min-1 10(-4)/(pmol/L)]; P less than 0.01), and lesser second phase beta-cell responsiveness to glucose (mean phi 2: Y = 18.5 +/- 3.6; E = 8.7 +/- 2.7 (microU/mL).min-2/(mg/dL) [2390 +/- 465 vs. 1120 +/- 349 (pmol/L).min-2/(mmol/L)]; P less than 0.05). A maximum improvement in Kg and S1 occurred at 41% carbohydrate feeding in the young men, whereas in the elderly men there was a significant increase in both of these parameters while eating the very high (85%) carbohydrate diet. Thus, the difference in glucose tolerance between groups was corrected by the very high carbohydrate diet (mean Kg: Y = 2.2 +/- 0.2%; E = 2.0 +/- 0.3%/min; P greater than 0.05), as was the age-related difference in insulin sensitivity (mean S1: Y = 5.6 +/- 1.2; E = 4.4 +/- 1.3 min-1 10(-4)/(microU/mL) [0.78 +/- 0.17 vs. 0.61 +/- 0.18 min-1 10(-4)/(pmol/L)]; P greater than 0.5).(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1988

Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs.

To determine which test of islet function is the most sensitive indicator of subclinical beta-cell loss, we studied six conscious dogs before and 1 and 6 wk after removal of the splenic and uncinate lobes [64 +/- 2% pancreatectomy (PX)]. To assess hyperglycemic potentiation, acute insulin secretory responses (AIR) to 5 g i.v. arginine were measured at the fasting plasma glucose (FPG) level after PG was clamped at approximately 250 mg/dl and after PG was clamped at a maximally potentiating level of 550-650 mg/dl. FPG levels were unaffected by PX (112 +/- 4 mg/dl pre-PX vs. 115 +/- 5 mg/dl 6 wk after PX, P NS). Similarly, basal insulin levels remained constant after PX (11 +/- 2 microU/ml pre-PX vs. 11 +/- 1 microU/ml 6 wk after PX, P NS). The AIR to 300 mg/kg i.v. glucose decreased slightly from 42 +/- 9 microU/ml pre-PX to 32 +/- 5 microU/ml 6 wk after PX (P NS), and thus the beta-cell loss was underestimated. In contrast, insulin responses to arginine declined markedly after PX. The AIR to arginine obtained at FPG levels declined from 23 +/- 3 microU/ml pre-PX to 13 +/- 2 microU/ml 6 wk after PX (P = .04). The AIR to arginine obtained at PG levels of approximately 250 mg/dl declined even more, from a pre-PX value of 56 +/- 7 microU/ml to 21 +/- 4 microU/ml 6 wk after PX (P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance.

In this study, we found that the ratio of proinsulin to total immunoreactive insulin was much higher in 22 patients with Type 2 (non-insulin-dependent) diabetes mellitus than in 28 non-diabetic control subjects of similar age and adiposity (32 +/- 3 vs 15 +/- 1%, p less than 0.001). In addition, the arginine-induced acute proinsulin response to total immunoreactive insulin response ratio was greater in diabetic patients (n = 10) than in control subjects (n = 9) (8 +/- 2 vs 2 +/- 0.5%, p = 0.009), suggesting that increased islet secretion per se accounted for the increased ratio of proinsulin to immunoreactive insulin. One explanation for these findings is that increased demand for insulin in the presence of islet dysfunction leads to a greater proportion of proinsulin secreted from the B cell. We tested this hypothesis by comparing proinsulin secretion before and during dexamethasone-induced insulin resistance in diabetic patients and control subjects. Dexamethasone treatment (6 mg/day for 3 days) raised the proinsulin to immunoreactive insulin ratio in control subjects from 13 +/- 2 to 21 +/- 2% (p less than 0.0001) and in diabetic patients from 29 +/- 5 to 52 +/- 7% (p less than 0.001). Dexamethasone also raised the ratio of the acute proinsulin response to the acute immunoreactive insulin response in control subjects from 2 +/- 0.5 to 5 +/- 2% (p = 0.01) and in diabetic patients from 8 +/- 2 to 14 +/- 4% (p = NS), suggesting that the dexamethasone-induced increment in the basal ratio of proinsulin to immunoreactive insulin was also due to increased secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Arginine↗
PubMed1987

The role of dietary carbohydrate in the decreased glucose tolerance of the elderly.

In this study we have attempted to evaluate the role of dietary carbohydrate (CHO) in the decreased glucose tolerance of aging. Eighteen healthy young (mean age, 27 +/- 1 standard error of the mean) (SEM) and 18 old (71 +/- 1 SEM) subjects matched for relative weight and socioeconomic group were studied. Oral glucose tolerance tests were performed while eating ad lib diet and after being given high (85%), medium (45%), and low (20% to 30%) CHO formula diets for at least three days. A three- to seven-day food record was used to determine the major nutrients including CHO and fiber intake in the ad lib diet at home. Our older subjects consumed significantly less total calories and slightly less carbohydrate but there was no difference in dietary fiber, protein, and fat intake. When studies were performed on matched CHO diets, decreased glucose tolerance was present in the older group. However, the mechanism(s) involved may vary with dietary CHO and with age. During the low CHO formula diet and the medium CHO ad lib diet, impaired insulin secretion was prominent in the elderly but was not present in the young. During the high CHO formula diet, insulin response was adequate in both old and young, but decreased glucose tolerance persisted in the older group, suggesting that insulin resistance may be the major contributing factor. We conclude that decreased glucose tolerance in the elderly is modified by CHO intake, but is present even when dietary CHO variability is acutely controlled.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1987

Reduced effect of experimental peripheral hyperinsulinemia to elevate cerebrospinal fluid insulin concentrations of obese Zucker rats.

To test the effect of chronic hyperinsulinemia on cerebrospinal fluid (CSF) insulin concentrations in the obese (fafa) Zucker rat, obese and heterozygote lean (Fafa) rats were infused peripherally with insulin or vehicle for 6 days. Both basal levels and the increase of plasma immunoreactive insulin (IRI) were greater in fafa (increase = 713 microU/ml) than in Fafa (increase = 392 microU/ml) rats, P less than 0.0001. Vehicle-infused fafa rats had higher CSF IRI levels than did vehicle-infused Fafa rats (4.3 +/- 1.2 microU/ml vs. 1.5 +/- 0.4 microU/ml, P less than 0.01). CSF IRI was elevated in both insulin-infused groups (P less than 0.001). After insulin infusion Fafa rats had higher CSF IRI levels than did fafa rats (Fafa: 10.0 +/- 1.8 microU/ml vs. fafa: 7.1 +/- 0.1 microU/ml). In contrast to the effect of insulin infusion on plasma IRI, the increase of CSF IRI was greater in Fafa rats (8.5 microU/ml) than in fafa rats (4.0 microU/ml, P less than 0.001). Uptake of insulin from the periphery to the CSF therefore appears to be reduced in obese fafa Zucker rats compared to lean Fafa controls.

Animals↗
PubMed1987

Cerebrospinal fluid insulin levels increase during intravenous insulin infusions in man.

We hypothesized that plasma insulin crosses the blood-cerebrospinal fluid (CSF) barrier and, as people gain weight, provides a physiological feedback signal to the central nervous system to inhibit food intake and further weight gain. However, it has not been demonstrated in man that insulin can enter the CSF from peripheral blood. To test whether increases in plasma insulin result in elevated CSF immunoreactive insulin (IRI) levels, we infused insulin iv in varying amounts approximating postprandial levels in eight normal subjects for 4.5 h. Euglycemia was maintained [88 +/- 3 (+/- SEM) mg/dl] by means of a variable glucose infusion. Samples were obtained every 30 min for measurements of insulin in peripheral plasma and insulin in lumbar CSF. Plasma IRI increased from a mean basal level of 12 +/- 1.2 microU/ml to a mean (during the 180- to 270-minute period) of 268 +/- 35 microU/ml. CSF IRI increased in all subjects during the infusion from a mean basal level of 0.9 +/- 0.1 microU/ml to a mean (during the 180- to 270-min period) of 2.8 +/- 0.4 microU/ml (P less than 0.006). By contrast, CSF IRI in two subjects who received an infusion of 0.9% saline did not increase. In summary, CSF insulin concentrations increased during peripheral infusions of insulin. This is the first demonstration in man that plasma insulin gains access to CSF and indicates a mechanism whereby peripheral insulin could provide a feedback signal to the central nervous system.

Adult↗
PubMed1987

Relationship of islet function to insulin action in human obesity.

To analyze B-cell mechanisms in obesity, we measured the relationship (slope of potentiation) between glucose levels and acute insulin responses (AIR) to isoproterenol or arginine in nondiabetic subjects ranging from lean to markedly obese. Obese men (n = 9) had higher AIRs to isoproterenol than lean men (n = 11) at basal glucose levels [52 +/- 9 (SEM) vs. 32 +/- 5 microU/mL; P less than 0.05], and the difference increased as the ambient glucose level was raised (at 230 mg/dL; 263 +/- 22 vs. 140 +/- 21 microU/mL; P less than 0.0008). The individuals' slopes of glucose potentiation of AIR to isoproterenol were positively correlated with their excess weight (r = 0.72; P less than 0.001). Similar results were found when arginine was used as the secretagogue in other men and in women; the slope of potentiation was positively correlated with excess weight in both men and women (both P less than 0.005), although the effect of excess weight on slope was 51% greater among men (P less than 0.03). An independent measurement of insulin sensitivity (the Bergman SI) was made in the women. The potentiation slope was inversely correlated with SI (P less than 0.0001), indicating that the effect of obesity on insulin secretion is correlated with insulin resistance. These results characterize one mechanism contributing to the hyperinsulinemia of obesity and highlight the importance of considering the prevailing insulin sensitivity when assessing islet function.

Adult↗
PubMed1986

Localization of 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography.

In vitro autoradiography and computer video densitometry were used to localize and quantify binding of 125I-insulin in the hypothalamus of the rat brain. Highest specific binding was found in the arcuate, dorsomedial, suprachiasmatic, paraventricular and periventricular regions. Significantly lower binding was present in the ventromedial nucleus and median eminence. The results are consistent with the hypothesis that insulin modulates the neural regulation of feeding by acting at sites in the hypothalamus.

Animals↗
PubMed1986

Intraventricular bombesin can decrease single meal size in the baboon.

We have reported that intravenous bombesin decreases single meal size in a dose-dependent manner. The present study tests whether intraventricular bombesin is also effective in decreasing single meal size. Doses of bombesin (0.1-4 micrograms/kg) were administered both intravenously and intraventricularly. A median dose of 1 microgram/kg bombesin decreased 30 min meal size about 50%, whereas a median dose of 1 microgram/kg given intravenously only decreased meal size 25%. We conclude that bombesin given centrally in the baboon can decrease meal size and that this effect does not appear to be due to leakage into the periphery.

Animals↗
PubMed1986

Intraventricular insulin reduces food intake and body weight of lean but not obese Zucker rats.

Porcine insulin (2 mU/rat/day) and its saline vehicle were infused into the third cerebral ventricle of female lean or obese Zucker rats using 14-day osmotic minipumps. Lean rats receiving saline (N = 6) gained 14 +/- 3 g over the 14 days, whereas lean rats receiving insulin (N = 7) lost 12 +/- 4 g over the same interval (p less than 0.01). The average total food intake of the insulin-infused group was decreased by 14% (p less than 0.05) as compared with that of the saline-infused group. The decreased caloric consumption was adequate to account for the body weight loss. Insulin infusion had no effect on food intake or body weight of the obese rats relative to their saline-infused controls (change in body weight: saline (N = 5), -14 +/- 23 g; insulin (N = 7), +3 +/- 14 g). These results suggest that genetically obese Zucker rats have reduced sensitivity to insulin in the central nervous system. We propose that this phenomenon may participate in the development and maintenance of hyperphagia and obesity in these animals.

Animals↗
PubMed1986

Effect of fasting interval on CCK-8 suppression of food intake in the baboon.

Baboons were infused intravenously for 5 min with the octapeptide of cholecystokinin (CCK-8) after either a 16.5- or 3.5-h fast. After a 3.5-h fast, food intake was significantly suppressed over the ensuing 30 min by 2 micrograms/kg of CCK-8 (-156 +/- 34 kcal compared with control days, P less than 0.02) and by 4 micrograms/kg of CCK-8 (-257 +/- 31 kcal, P less than 0.01). In contrast, CCK-8 had no reliable effect on food intake after the same baboons had been fasted for 16.5 h (2 micrograms/kg: -93 +/- 40 kcal, P greater than 0.05; 4 micrograms/kg: -30 +/- 82 kcal, P greater than 0.05). There was no reliable effect of 1 microgram/kg of CCK-8 on food intake at either deprivation interval. CCK-8 infusions resulted in a small increase of fasting plasma immunoreactive insulin (IRI); this effect was not related to either dose or deprivation length. Postprandial IRI and glucose concentrations were significantly suppressed by CCK-8 independently of its effect on food intake. Thus, after a 16.5-h fast, 4 micrograms/kg of CCK-8 decreased postprandial IRI from 145 +/- 65 to 29 +/- 4 microU/ml (P less than 0.01) and glucose from 101 +/- 5 to 80 +/- 3 mg/dl (P less than 0.02), despite no concomitant effect on food intake. Similar suppression of plasma IRI and glucose were observed after infusions of 1 and 2 micrograms/kg in 16.5-h-fasted animals. All doses of CCK-8 (1, 2, and 4 micrograms/kg) suppressed postprandial IRI and glucose after a 3.5-h fast.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons.

We have previously reported that intravenous administration of the octapeptide of cholecystokinin (CCK-8) is more effective in reducing single meal size in baboons at noontime than in the morning. We have also reported that immunoreactive insulin levels in the cerebrospinal fluid (CSF) are elevated after animals have recently eaten. To test whether elevated CSF insulin levels can alter the efficacy of intravenous CCK to reduce meal size we administered subthreshold doses of CCK-8 to baboons infused with either synthetic CSF or CSF and insulin (100 microU X kg-1 X day-1) via the cisterna magna. Intravenous CCK-8 alone reduced 30-min meal size from 504 +/- 121 to 378 +/- 113 kcal (n = 7, P = NS). Chronic intracisternal insulin infusion enhanced CCK-8's suppressive effects such that 30-min meal size was reduced from 544 +/- 74 to 240 +/- 108 kcal (n = 7, P less than 0.005). Intracisternal insulin infusion had no significant effect on total food intake, basal plasma insulin and glucose levels, or postprandial plasma insulin and glucose levels. These findings suggest that central insulin may contribute to food intake regulation by modulating the ability of brain-gut peptides to alter single meal size.

Animals↗
PubMed1986

Identification of binding sites for an insulin-like growth factor (IGF-I) in the median eminence of the rat brain by quantitative autoradiography.

The microanatomical location of IGF-I binding in the rat brain was determined by in vitro autoradiography with slide-mounted sections of frozen brain. Sections incubated in 0.1 nM [125I]-iodo-IGF-I produced a dense grain concentration in regions of the autoradiographic image corresponding to the external palisade zone of the median eminence; other hypothalamic regions were not so heavily labeled. This reaction was significantly reduced in the presence of 100 nM IGF-I. Measurement of binding by computer digital image analysis of autoradiographic images showed that specific binding for IGF-I in the median eminence was 41.3 +/- 8 X 10(-3) fmol/mm2 (mean +/- SEM); nonspecific binding was 11.9 +/- 1.8 X 10(-3) fmol/mm2. In contrast, specific binding to other hypothalamic regions was uniformly lower. In a separate experiment, 1000 nM unlabeled insulin was added. Without insulin, specific binding was 23 +/- 0.9 X 10(-3) fmol/mm2; nonspecific binding was 8 +/- 0.5 X 10(-3) fmol/mm2. In the presence of 1000 nM unlabeled insulin, specific binding for [125I]-iodo-IGF-I was 23 +/- 1 X 10(-3) fmol/mm2. The results suggest that a high concentration of receptors for an IGF-I-like molecule is present in the median eminence.

Animals↗
PubMed1986

Plasma catecholamines, dietary carbohydrate, and glucose intolerance: a comparison between young and old men.

Catecholamines play an important role in glucose homeostasis. This study was designed to determine whether circulating catecholamine changes in the elderly play a role in the glucose intolerance of aging and whether these changes are related to dietary carbohydrate intake. Plasma catecholamines (epinephrine and norepinephrine) and glucose were measured before and for 2 h after the administration of 100 g oral glucose in both 18 young (age, 18-39 yr) and 20 old (age, 60-82 yr) normal men during ad libitum home diet and after 3-day weight-maintaining, high or low carbohydrate formula diets in the Clinical Research Center. The elderly men had higher plasma norepinephrine levels before and after oral glucose than the young men even when eating matched formula diets. Plasma epinephrine levels were similar and decreased significantly after oral glucose in both groups. There was no relationship between catecholamine levels and degree of glucose tolerance. A high carbohydrate diet improved glucose tolerance in both old and young subjects. However, changes in dietary carbohydrates were not associated with consistent changes in plasma catecholamines. Therefore, we conclude that 1) glucose intolerance of aging cannot be explained by changes in plasma catecholamines, 2) the age-related increase in plasma norepinephrine is unrelated to dietary carbohydrate intake, and 3) there is no effect of age on suppression of plasma epinephrine after oral glucose administration.

Adolescent↗