Biomedical subjects

C A Stuart

Publications and source records attributed to C A Stuart.

At least 37 records · Page 2Linked to original sources

PubMed1990

Effect of dietary protein on bed-rest-related changes in whole-body-protein synthesis.

To determine whether increasing dietary protein could exert a beneficial effect on bed-rest-related protein catabolism, two groups of normal subjects were subjected to 7 d of bed rest while taking isocaloric diets containing either 0.6 or 1.0 g protein.kg body wt-1.d-1. Whole-body-leucine turnover, leucine oxidation, and nonoxidative leucine disappearance were measured by use of a constant infusion of 1-13C-leucine. Before bed rest, the higher-protein diet resulted in a 14% decrease in whole-body-leucine turnover and a 28% decrease in leucine oxidation, but net nonoxidative leucine disappearance was not different on the two diets. A 24% decrease in nonoxidative leucine disappearance was seen in subjects assigned to the lower-protein diet, who had been on bed rest, but on the higher-protein diet, leucine kinetics were unchanged by bed rest. Bed rest does not cause an increase in whole-body-protein breakdown, but decreased whole-body-protein synthesis is demonstrable when dietary protein is low. This decrease is prevented by a higher dietary amount of protein.

Adult↗

PubMed1990

Whole body and plasma protein synthesis in exercise and recovery in human subjects.

The effect of 4 h of exercise at 40% of maximal oxygen consumption (VO2 max) on protein metabolism was assessed in normal volunteers maintained on a diet containing 42 kcal.kg-1.day-1 and either 0.9 or 2.5 g protein.kg-1.day-1. Primed constant infusions of [1,2-13C]-leucine and [15N]glycine enabled the quantitation of whole body protein turnover and also the fractional synthetic rates (FSR) of albumin, fibrinogen, and fibronectin. In subjects who did not exercise, the fractional synthetic rates (%/day) on normal and high-protein intakes, respectively, were as follows: albumin, 10 +/- 1 and 9 +/- 1; fibrinogen, 21 +/- 3 and 18 +/- 1; and fibronectin, 31 +/- 3 and 34 +/- 3. Neither exercise nor recovery had an effect of whole body protein turnover or on albumin FSR, but the FSR of fibronectin was significantly elevated at the end of exercise, and fibrinogen was significantly elevated in recovery. Dietary protein intake had no major effect on the response to exercise. Thus, in response to exercise, there is a stimulation of the synthesis of some acute phase proteins, which may be a mechanism whereby nitrogen resulting from muscle protein breakdown is spared.

Amino Acids↗

PubMed1990

Effect of exercise and recovery on muscle protein synthesis in human subjects.

Previous studies using indirect means to assess the response of protein metabolism to exercise have led to conflicting conclusions. Therefore, in this study we have measured the rate of muscle protein synthesis in normal volunteers at rest, at the end of 4 h of aerobic exercise (40% maximal O2 consumption), and after 4 h of recovery by determining directly the rate of incorporation of 1,2-[13C]leucine into muscle. The rate of muscle protein breakdown was assessed by 3-methylhistidine (3-MH) excretion, and total urinary nitrogen excretion was also measured. There was an insignificant increase in 3-MH excretion in exercise of 37% and a significant increase (P less than 0.05) of 85% during 4 h of recovery from exercise (0.079 +/- 0.008 vs. 0.147 +/- 0.0338 mumol.kg-1.min-1 for rest and recovery from exercise, respectively). Nonetheless, there was no effect of exercise on total nitrogen excretion. Muscle fractional synthetic rate was not different in the exercise vs. the control group at the end of exercise (0.0417 +/- 0.004 vs. 0.0477 +/- 0.010%/h for exercise vs. control), but there was a significant increase in fractional synthetic rate in the exercise group during the recovery period (0.0821 +/- 0.006 vs. 0.0654 +/- 0.012%/h for exercise vs. control, P less than 0.05). Thus we conclude that although aerobic exercise may stimulate muscle protein breakdown, this does not result in a significant depletion of muscle mass because muscle protein synthesis is stimulated in recovery.

Adult↗

PubMed1990

Insulin infusion acutely augments ovarian androgen production in normal women.

Euglycemic insulin clamp studies were performed at a sustained physiological insulin concentration of 420 +/- 35 pmol/L (60 +/- 5 muU/mL) in five women who had undergone bilateral oophorectomy and in five intact normal women during the follicular phase of their menstrual cycles to determine the relative contributions of the ovary and adrenal glands in insulin-related augmentation of androgen secretion. Normal women increased their plasma dehydroepiandrosterone (DHEA) concentration by 7.3 +/- 0.4 nmol/L (to 239% +/- 15% of basal), but in oophorectomized women DHEA increased by 1.4 +/- 0.4 nmol/L (to 135% +/- 15% of basal). Thus, the acute response in DHEA to insulin infusion in women without ovaries was only 20% of that seen in intact women. The androstenedione response in oophorectomized subjects was 27% of that seen in controls. We conclude that the insulin stimulation of androgen production occurs predominately at an ovarian site.

Adrenal Glands↗

PubMed1990

Receptors for insulin and IGF-I in bovine lens epithelium.

The presence of insulin receptors has not yet been established in lens epithelial cells. Our goal was to understand the involvement of insulin in lens pathology, especially diabetic cataractogenesis. As a first step in this process, we evaluated the presence of insulin receptors in bovine lens epithelium. Insulin bound to insulin receptor with a high affinity (KD 7.0 nM), although this binding of insulin to its receptor could be replaced by IGF-I (KD 41 nM). Similarly IGF-I binding to IGF-I receptor (KD 0.38 nM) could be inhibited by insulin (KD 53.7 nM). SDS-PAGE and subsequent autoradiography of affinity labeled insulin receptor show the presence of a 130 kDa band, indicating that the lens epithelium insulin receptor may be similar to insulin receptors isolated from other tissues.

Affinity Labels↗

PubMed1989

Dexamethasone effects on creatine kinase activity and insulin-like growth factor receptors in cultured muscle cells.

We examined the effects of dexamethasone on creatine kinase (CK) activity and insulin-like growth factor I (IGF-I) binding in two skeletal muscle-derived cell lines (mouse, C2C12; rat, L6) and in one cardiac muscle-derived cell line (rat, H9c2). Dexamethasone treatment during differentiation of cultured cells caused a dose-dependent increase in CK activity as well as an increase in the degree of myotube formation in C2C12 and L6, whereas H9c2 cells did not exhibit significant CK activities during culture or dexamethasone treatment. Dexamethasone treatment of C2C12 did not stimulate proliferation in differentiating cultures, but a dose-dependent increase in the number of nuclei was observed for L6 concomitant with increased CK activity. In L6 the increased CK activity may therefore reflect a dose-dependent increase in proliferation. Short-term (48 hr) treatment of C2C12 with dexamethasone (20 nM) did not appear to alter myoblast fusion but reversibly increased CK activity. In C2C12 the observed increase in CK, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities with dexamethasone treatment suggest modulation of protein expression and/or turnover. Although the data for dexamethasone effects on CK activities varied in each of the cell lines, consistent behavior was observed in all three cell lines when IGF-I binding was examined. IGF-I binding to dexamethasone-treated cells (50 nM for 24 hr the day prior to confluence) resulted in an increased number of available binding sites, with no effect on the binding affinities. Affinity cross linking and autoradiography indicated that the increase in IGF-I binding was the result of dexamethasone up-regulation of type I IGF receptors. Our data for all three muscle cell lines suggest that similar heterologous hormone receptor modulation of type I IGF receptor sites occurs with dexamethasone treatment.

Alanine Transaminase↗

PubMed1989

Steroid biosynthesis in the Sertoli-Leydig cell tumor: effects of insulin and luteinizing hormone.

In vitro steroid production by a virilizing Sertoli-Leydig cell tumor of the ovary was studied. For comparison, stromal tissue from the opposite normal ovary was also incubated under similar conditions. The tumor fragments secreted significantly more testosterone (527 +/- 168 versus 48 +/- 29 pg/mg tissue, p less than 0.001), androstenedione (1188 +/- 400 versus 40 +/- 10 pg/mg tissue, p less than 0.001), and dehydroepiandrosterone (419 +/- 132 versus 73 +/- 25 pg/mg tissue, p less than 0.004) than that of normal ovarian stroma. Measurement of steroids in the ovarian venous serum draining the tumor indicated a peripheral ovarian gradient for both delta 4 and delta 5 steroids. Incubation of tumor fragments with luteinizing hormone alone resulted in a significant increase in the secretion of androstenedione and dehydroepiandrosterone (p less than 0.05). Addition of insulin to luteinizing hormone resulted in significantly greater release of androstenedione than that of treatment with luteinizing hormone alone (p less than 0.04). Addition of insulin had no effect on the release of dehydroepiandrosterone. Luteinizing hormone and insulin, either alone or in combination, failed to produce any change in the secretion of testosterone. We conclude that (1) increased testosterone secretion by Sertoli-Leydig cell tumor resulted from increased availability of precursors from both delta 4 and delta 5 pathways; (2) the tumor was responsive to luteinizing hormone with an increase in the secretion of androstenedione and dehydroepiandrosterone; (3) insulin acts synergistically with luteinizing hormone to increase secretion of androstenedione; (4) the tumor has specific binding sites for insulin; and (5) the increased levels of insulin and luteinizing hormone in polycystic ovarian disease may play a role in the pathogenesis of Sertoli-Leydig cell tumor.

Adult↗

PubMed1989

Differentiation between septic and postburn insulin resistance.

Sepsis and extensive burn injury produce clinical syndromes characterized in part by "insulin resistance," but it is unclear if these insulin resistant states are identical. To test if the maximal biological effectiveness of insulin is altered in septic or burned patients, eight septic patients and eight nonseptic patients recovering from severe burn injury were studied using the hyperinsulinemic eukalemic euglycemic clamp technique. Compared with bed-rested controls, the septic patients showed an insulin-induced plasma clearance of potassium, which was 183% higher (P less than .001), and a concomitant glucose clearance, which was 52% lower (P less than .001). Nonseptic burn patients also had a 91% increase in potassium clearance (P less than .05), but their maximal insulin-stimulated glucose uptake was not different from that of bedrested controls. When septic patients were compared with their nonseptic burned counterparts, there was no difference in potassium clearance in response to insulin, but glucose uptake by the septic patients was 47% lower (P less than .001). Insulin infusion completely suppressed hepatic glucose production in both septic patients and in nonseptic burn patients. The percent of whole body glucose uptake that was oxidized was not different between the septic patients and the nonseptic postburn patients in both the basal and insulin-stimulated states (38% and 51% v 38% and 42%, respectively). It is concluded that septic and postburn insulin resistance differ in that peripheral glucose uptake in sepsis, but not nonseptic burn injury, is refractory to pharmacologic insulin stimulation, whereas in both states insulin effectively stimulates potassium uptake.

Adult↗

PubMed1989

Prevalence of acanthosis nigricans in an unselected population.

PURPOSE: The intent of this study was to determine, in an unselected population, the prevalence of the hyperinsulinemia-associated skin lesion, acanthosis nigricans. SUBJECTS AND METHODS: The posterior neck of every child in the sixth and eighth grades of the public schools of Galveston, Texas, was personally examined by the investigators during a state-mandated school health survey. A total of 1,412 children were examined. RESULTS: The data for each child examined included the absence or presence of acanthosis nigricans, height, weight, age, sex, and ethnic background. A subset of the children with the skin lesion also had fasting plasma insulin levels measured. Acanthosis nigricans was present in 7.1% of the 1,412 children examined. The skin lesion was equally distributed between boys and girls and was most common among children with severe obesity. The condition was present in two of 440 white non-Hispanics, 19 of 343 Hispanics, and 80 of 601 blacks examined. The fasting plasma insulin concentrations measured in some of these children and in previously evaluated subjects strongly correlate with the presence and severity of the acanthosis nigricans skin lesion. CONCLUSIONS: This skin lesion is much more common than previously believed and has a dramatic ethnic predisposition. We conclude that the high prevalence of this skin lesion further suggests that insulin resistance and hyperinsulinemia, with all of their serious medical implications, are also highly prevalent.

Acanthosis Nigricans↗

PubMed1989

Autophosphorylation of cultured skin fibroblast insulin receptors from patients with severe insulin resistance and acanthosis nigricans.

The severe insulin resistance with acanthosis nigricans seen in young women without insulin-receptor autoantibodies is characterized by hyperinsulinemia and decreased in vivo responsiveness to insulin. We evaluated the potential cellular defects in insulin-receptor binding and autophosphorylation in 12 subjects with this syndrome. When evaluated as a group, insulin binding to freshly isolated monocytes was 55% that of controls. Specific binding of insulin to skin fibroblasts in monolayer culture was 49% that of controls. Maximal insulin-stimulated receptor autophosphorylation was only 27% that of controls. Individual data demonstrated that the diminished autophosphorylation activity was out of proportion to the diminished fibroblast insulin binding in cell lines from most subjects and was less than 50% of the predicted activity in 6 of the 12 studied cell lines. These data are consistent with genetically determined defects leading to diminished numbers of cell surface insulin receptors with intact tyrosine kinase autophosphorylation in many of our cell lines. However, in at least half, there appeared to be an additional defect beyond insulin binding, resulting in a disproportionate decrease in insulin-sensitive phosphorylation of the insulin-receptor beta-subunit.

Acanthosis Nigricans↗

PubMed1988

High affinity antibody from hen's eggs directed against the human insulin receptor and the human IGF-I receptor.

Large quantities of high affinity antibodies directed against the human insulin receptor and the human insulin-like growth factor-I (IGF-I) receptor were obtained from hen's eggs. Hens were immunized with human placental membranes and human liver membranes by intramuscular injections. Specific antibodies to the receptors were demonstrated in serum and egg yolks at 5 weeks and these antibodies presisted for at least 6 months. Antibodies from egg yolks were purified by the polyethylene glycol precipitation technique of Polson et al. The eggs provided the equivalent of about 450 ml of immunized serum per month per bird. The purified antibodies were approximately equally reactive with receptors for insulin or IGF-I. Antibodies immunoprecipitated affinity-labeled receptors, inhibited binding of each ligand, and were capable of stimulating 2-deoxyglucose uptake in rat adipocytes and thymidine incorporation in cultured fibroblasts. The presence of antibodies directed against the IGF-I receptor in those hens immunized with human liver membranes was unexpected, since liver membranes possess little or no IGF-I binding activity. We conclude that antibodies against human antigens may be relatively easily obtained by immunization of hens and purification of those antibodies from eggs.

Animals↗

PubMed1988

Characterization of a novel insulin receptor from stingray liver.

The insulin receptor from the liver of stingray, a cartilaginous fish, has characteristics which are in marked contrast to those of the mammalian insulin receptor. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cross-linked, affinity-labeled stingray insulin receptor shows an apparent molecular mass of 210 kDa for the intact receptor. Reduction with mercaptoethanol resulted in no alteration in the apparent size of the stingray insulin receptor. Gel filtration studies of Triton X-100 solubilized stingray insulin receptor demonstrated an apparent Stokes radius of 7.6 nm. Ultracentrifugation sucrose gradient studies of cross-linked affinity labeled stingray receptor resulted in determination of a sedimentation coefficient of 13 S. Both of these parameters were greater than simultaneously obtained data for the human insulin receptor (7.2 nm and 11 S, respectively). Unlabeled insulin competed with binding of 125I-insulin and 125I-insulin growth factor (IGF) I with a half-maximal concentration of 1 nM for either. Unlabeled IGF I and II also competed, but were 4-5-fold less potent than insulin. It was found that not only did IGF I bind to the 210-kDa material, but both insulin and IGF I stimulated phosphorylation of a 210-kDa material which was immunoprecipitable by a polyclonal insulin receptor antibody. Elution of this material from the gel followed by hydrolysis and thin layer chromatography demonstrated that the 210-kDa material was specifically phosphorylated on tyrosine only. These data suggest that the insulin receptor from stingray liver is a dimer made up of 2 identical subunits of about 210 kDa size which contain both binding regions and insulin-stimulated tyrosine kinase. Specificity studies suggest that the stingray insulin receptor may represent a phylogenetic position prior to the evolutionary divergence of insulin and the insulin-like growth factors.

Affinity Labels↗

PubMed1988

Bed-rest-induced insulin resistance occurs primarily in muscle.

Treatment of trauma victims and patients with severe illness may contribute to their metabolic derangements by severely restricting physical activity. We sought to quantitate the impact of absolute bed rest alone on insulin regulation of glucose metabolism in six healthy subjects. Six to seven days of strict bed rest resulted in moderate deterioration in oral glucose tolerance and increased both fasting plasma insulin concentration and the insulin response to an oral glucose challenge by more than 40%. Euglycemic insulin clamp studies demonstrated the development of resistance to insulin's stimulation of whole-body glucose utilization. This change was characterized by a rightward shift of the insulin dose-response curve (insulin concentration at which 50% of maximal stimulation occurred was 45 +/- 3 (SE) microU/mL in the base line period and 78 +/- 8 microU/mL after seven days of bed rest, P less than .01) with little alteration in the maximal response in the rate of glucose uptake (baseline 15.4 +/- 1.4 mg/kg.min and bed rest 14.0 +/- 1.3 mg/kg.min). In contrast to the shift of sensitivity of whole-body glucose utilization to insulin, suppression of hepatic glucose output by insulin was unchanged by seven days of bed rest. Insulin binding to circulating mononuclear cells was not changed by bed rest. These studies demonstrate that the limited physical activity dictated by bed rest for as little as seven days is associated with substantial resistance to insulin's effects on glucose metabolism. Further, the data suggest that these effects occur primarily in skeletal muscle with little change in insulin action on the liver.

Adult↗

PubMed1988

Insulin responsiveness of protein metabolism in vivo following bedrest in humans.

To test the influence of bedrest on insulin regulation of leucine metabolism, six normal young men were subjected to a five-step hyperinsulinemic euglycemic clamp before and after 7 days of strict bedrest. A primed-constant infusion of [1-13C]leucine at 0.12 +/- 0.02 mumol.kg-1.min-1 was used. Before bedrest, the basal rate of appearance (Ra) of intracellular leucine and leucine oxidation were 2.79 +/- 0.17 and 0.613 +/- 0.070 mumol.kg-1.min-1, respectively. Insulin caused a dose-dependent reduction of the intracellular leucine Ra and leucine oxidation to a minimum of 1.64 +/- 0.08 and 0.322 +/- 0.039 mumol.kg-1.min-1, respectively, in nonbedrested subjects (P less than 0.001). Insulin also caused a dose-dependent reduction of plasma leucine concentration from 95 +/- 4 to 38 +/- 2 mumol/l (P less than 0.001). After bedrest, subjects exhibited decreased glucose tolerance and increased endogenous insulin secretion, but basal and insulin-suppressed intracellular leucine Ra and leucine oxidation rates were not different from control. Magnetic resonance imaging of the back and lower extremities revealed a 1-4% decrease in muscle volume and a 2-5% increase in fat volume secondary to bedrest. Bedrest also resulted in a negative nitrogen balance as compared with the control period, with an average cumulative loss of 6.3 g of nitrogen after 6 days. Urinary 3-methyl-L-histidine excretion was unchanged by bed rest. Thus because negative nitrogen balance and skeletal muscle atrophy occurred in six rested subjects in the absence of changes in the two indices of protein breakdown used in this study (3-methyl-L-histidine release and leucine release), it seems likely that muscle protein synthesis was inhibited.

Adipose Tissue↗

PubMed1988

A monoclonal antibody to the type 1 insulin-like growth factor and insulin receptors stimulates deoxyribonucleic acid synthesis in human and murine fibroblasts.

Insulin-like growth factor I (IGF-I) and insulin are polypeptide hormones that stimulate their cellular responses by binding to specific cell membrane receptors. These receptors, while chemically distinct, have similar structural and functional characteristics. This manuscript describes the production and characterization of a monoclonal antibody that binds to both type I IGF and insulin receptors. This antibody did not inhibit hormone binding to either receptor type, but stimulated DNA synthesis in both human and murine fibroblasts. Ten BALB/c-BYJ mice were immunized with human placental membrane fragments, and their splenic lymphocytes were fused with SP2 AG0 mouse myeloma cells. Of approximately 3000 hybridoma clones thus obtained, 1 viable clone, designated V3,8 D7, was found to produce an antibody directed against the type I IGF receptor. Solubilized radiolabeled placental membranes immunoprecipitated with affinity-purified antibody and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing conditions revealed bands with relative molecular masses corresponding to the nonreduced intact receptor (approximately 350 x 10(3], the alpha-subunit (130-140 x 10(3], and the beta-subunit (90 x 10(3] of the type I IGF receptor. Clonal supernatant and affinity-purified antibody precipitated solubilized receptors affinity labeled with [125I]IGF-I. Antibody V3,8 D7 also precipitated solubilized placental membranes affinity labeled with [125I]insulin. However, solubilized receptors affinity purified by the monoclonal antibody bound IGF-I much better than insulin, suggesting that this antibody has a higher affinity for the type I IGF receptor than for the insulin receptor. Affinity-purified antibody did not inhibit the binding of IGF-I or insulin to receptors on human placental membranes, suggesting that it is directed against a site on the type I IGF and insulin receptor not involved in hormone binding. However, affinity-purified monoclonal antibody stimulated DNA synthesis in human GM 498 and murine BALB/c-3T3 clone A 31 fibroblasts, as determined by [3H]thymidine incorporation. The combination of IGF-I and affinity-purified antibody did not increase thymidine incorporation above levels observed with either substrate alone, suggesting that these factors may be operating through a common mechanism. These results suggest that antibody V3,8 D7 can stimulate receptor responses by binding to a site on the type I IGF and/or insulin receptors that is not involved in hormone binding. These data support the concept that hormone receptors themselves possess the biological information required for stimulating specific cellular responses.

Animals↗

PubMed1988

Hyperinsulinemia and stromal luteinization of the ovaries in postmenopausal women with endometrial cancer.

Ovarian secretion of testosterone and androstenedione is increased in postmenopausal women with endometrial cancer, and insulin stimulates ovarian stromal androgen synthesis in vitro. We undertook this study to investigate whether women with endometrial cancer have increased serum immunoreactive insulin levels. Ten postmenopausal women with endometrial carcinoma and 10 postmenopausal women without cancer who matched the cancer patients in age, years since menopause, and percentage of ideal body weight were studied. The women with endometrial cancer had significantly higher fasting serum insulin levels than the normal women [mean, 187 +/- 26 (+/- SE) vs. 55 +/- 11 pmol/L; P less than 0.01]. The cancer patients had significantly higher insulin responses after glucose administration than normal women (sum of 1, 2, and 3 h postglucose values, 5545 +/- 1526 vs. 1444 +/- 156 pmol/L; P less than 0.02), even though their glucose responses were similar. Nests of luteinized cells, which were positive for testosterone by immunoperoxidase staining, were found in the ovarian stroma of 8 of the women with endometrial cancer, but in only 1 of those without cancer (P less than 0.01). Specific high affinity insulin receptors were demonstrable in the stroma of the postmenopausal ovaries. These results suggest that the frequency of stromal luteinization is increased in women with endometrial cancer and that insulin may play a role in the pathogenesis of this luteinization.

Adenocarcinoma↗

PubMed1988

Metabolic effects of hydrochlorothiazide and enalapril during treatment of the hypertensive diabetic patient. Enalapril for hypertensive diabetics.

To determine the effect of enalapril maleate and low-dose hydrochlorothiazide therapy on blood pressure and glucose and lipid homeostasis in hypertensive type II diabetic patients, we treated nine of these patients sequentially with placebo, hydrochlorothiazide (25 mg/d with supplemental potassium chloride), and enalapril (10 to 20 mg/d). Sitting blood pressure fell significantly and to comparable levels with both hydrochlorothiazide and enalapril monotherapy. Enalapril monotherapy was associated with a slight, but not significant, fall in fasting blood glucose levels and with a significant fall in hemoglobin A1c levels. This improved glucose homeostasis could not be explained satisfactorily by changes in peripheral insulin sensitivity or hepatic glucose output, determined with the euglycemic clamp technique, or by changes in fasting serum insulin levels or monocyte insulin binding. In these low doses, hydrochlorothiazide did not worsen glucose homeostasis. Serum total cholesterol levels were significantly lower with enalapril therapy than with hydrochlorothiazide therapy or with placebo, and serum high-density lipoprotein cholesterol and triglyceride levels did not change significantly with either treatment. Thus, by providing effective blood pressure control and beneficial metabolic effects, enalapril therapy appears ideal for treatment of hypertension in diabetic patients. Similarly, low-dose hydrochlorothiazide therapy appears to have fewer metabolic complications in these patients and is, therefore, a logical alternative to substitute for, or add to, enalapril therapy.

Adult↗

PubMed1987

Hyperinsulinemia and hyperandrogenemia: in vivo androgen response to insulin infusion.

The plasma androgen responses to multiple-dose insulin infusions were determined in six normal females, four normal males, five obese females, and in three females with severe insulin resistance, hirsutism, and acanthosis nigricans. During the insulin infusions, the plasma glucose concentrations were maintained at 85 +/- 1 mg/dL by variable infusions of dextrose. Plasma androstenedione was augmented by 27-39% at physiologic insulin concentrations in the normal subjects and the obese group, and by 25% at hyperinsulinemic levels in the insulin-resistant group with acanthosis nigricans. The increased androstenedione concentrations achieved in the normal females and obese females were similar to the hyperandrogenemic levels seen in the acanthotic subjects in the basal state. Plasma cortisol also increased in all groups from 19% in normal females to 135% in obese females during the insulin infusions, but these changes did not reach statistical significance. These studies suggest that hyperinsulinemia may play a pathogenic role in the hyperandrogenemia of polycystic ovarian disease.

Acanthosis Nigricans↗