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Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 109 records · Page 6Linked to original sources
PubMed1994

Malignancy-associated hypercalcaemia: resolution of controversies over vitamin D metabolism by a pathophysiological approach to the syndrome.

OBJECTIVE: Parathyroid hormone-related protein (PTHrP) is recognized as a major pathogenetic factor of humoral hypercalcaemia of malignancy but its action on vitamin D metabolism is controversial. Our aim was to study the relation between serum 1,25-dihydroxyvitamin D and humoral activity in malignancy-associated hypercalcaemia. DESIGN: Prospective, cross-sectional, single-centre study of patients with documented solid malignancies, hypercalcaemia and suppressed plasma PTH concentrations. PATIENTS AND METHODS: Vitamin D metabolites, PTH, nephrogenous cyclic AMP (N-cAMP), PTHrP and biochemical parameters of calcium and bone metabolism were measured in 39 patients with solid malignancies and hypercalcaemia and bone scans were performed. RESULTS: In 27 patients plasma PTHrP levels were elevated (69%) and in 9 patients (23%) serum 1,25-(OH)2D concentrations were not appropriately suppressed (> 92 pmol/l). Patients with plasma PTHrP levels below the upper limit of normal (< 1.6 pmol/l) had lower serum 1,25-(OH)2D concentrations than those with elevated levels (> 1.6 pmol/l) (47 +/- 6 vs 70 +/- 7 pmol/l, respectively; P < 0.04). Serum 1,25-(OH)2D concentrations were higher in patients with negative bone scans than in those with metastatic bone disease (80 +/- 9 vs 50 +/- 5 pmol/l; P < 0.01) and similar levels of plasma PTHrP. In the patients with negative bone scans there was a significant relation between plasma PTHrP and serum 1,25-(OH)2D (r = 0.51; P < 0.03) whereas there was no such correlation in those with a positive scan. CONCLUSION: Contrary to current belief, serum 1,25-(OH)2D concentrations are not generally suppressed in humoral hypercalcaemia of malignancy and PTHrP is a determinant of these levels in the absence of demonstrable bone metastases. These findings provide further insights into the pathophysiology of malignancy-associated hypercalcaemia and may help in the clinical management of these patients.

Aged↗
PubMed1994

Effect of insulin resistance, apoE2 allele, and smoking on combined hyperlipidemia.

Combined hyperlipidemia may result from the interaction of several metabolic and environmental factors. We explored to what extent fasting insulin concentration, apolipoprotein (apo) E2 frequency, and cigarette smoking explained the serum levels of triglyceride and high-density lipoprotein cholesterol (HDL-C) in patients with combined hyperlipidemia. Forty-nine untreated patients with combined hyperlipidemia were compared with 49 hypercholesterolemic patients who were matched for gender, age, and body mass index. All laboratory values were obtained after 9 weeks of standardized dietary intake and after an overnight fast. The patients with combined hyperlipidemia had a significantly higher (33 pmol/L, 50%) mean insulin concentration than matched hypercholesterolemic control subjects, indicating that the combined hyperlipidemic patients were more insulin resistant. However, the differences in the fasting insulin and triglyceride concentrations within the pairs were only slightly correlated (adjusted r = .29). The combined hyperlipidemic patients were also characterized by a higher frequency of apoE2 alleles (25% versus 6%) and smokers (41% versus 16%). In a matched multiple linear regression model, the differences in insulin concentration, apoE2 allele frequency, and smoking explained 12%, 8%, and 9%, respectively, of the mean paired difference in triglyceride concentration. The differences in insulin concentration or apoE2 allele frequency did not significantly explain the mean paired difference in HDL-C concentration, whereas smoking explained 17% of the difference. In conclusion, fasting insulin concentration, the presence of the apoE2 allele, and smoking may explain 30% of the hypertriglyceridemia and the low levels of HDL-C in nonobese patients with combined hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Alleles↗
PubMed1994

Growth hormone secretion in recently operated acromegalic patients.

GH secretion patterns were studied in 14 recently transsphenoidally operated patients by measuring GH concentrations in blood sampled every 10 min over 24 h with a highly sensitive time-resolved immuno-fluorescent assay. Plasma GH concentrations were analyzed with a discrete peak detection program (Cluster) and a multiparameter deconvolution technique. Diurnal variations were analyzed by cosinor analysis. Nine or 10 days after pituitary surgery all patients had a normal plasma insulin-like growth factor-I level, and GH levels were suppressed to below 1.25 micrograms/L in 13 patients and to 1.3 micrograms/L in 1 subject during an oral glucose tolerance test. As we found a highly significant difference in GH secretion between male and female controls, the results obtained in patients were compared with those in their gender- and age-matched controls. Patients with active acromegaly displayed a significantly higher number of deconvolution-estimated secretory bursts (31/24 h in males and 27/24 h in female patients). The estimated secretion rate per 24 h was 25 times greater in female acromegalics and 100 times greater in male acromegalics than that in the controls. In patients with active acromegaly, about 50% of the GH was secreted in a nonpulsatile fashion. In contrast, normal subjects and patients shortly after pituitary surgery secreted GH predominantly (> 99%) in a pulsatile manner. By deconvolution analysis, the mean plasma half-life of GH was 19.7 min in treated male patients and 19.5 min in treated female patients (P = NS vs. controls) estimated mean total GH production/day, 188 micrograms in males and 240 micrograms in females (P = NS vs. controls); number of secretory bursts/24 h, 19.3 in males and 21.9 in females (P = NS vs. controls). In addition, we could not establish any difference in pulse characteristics with Cluster analysis between surgically treated patients and their control subjects. The present data suggest that the basic abnormality of acromegaly resides in the pituitary gland rather than in the hypothalamus.

Acromegaly↗
PubMed1993

The pharmacokinetic and pharmacodynamic interactions of ramipril with propranolol.

We have studied the pharmacodynamic effects of ramipril, propranolol, and their combination, as well as the effect of propranolol on the pharmacokinetics of ramipril in 12 healthy men (age 24 (SD 6) y, weight 72 (7) kg). Propranolol and placebo, ramipril and placebo, or propranolol and ramipril were given orally for four days in a crossover, double-blind fashion. The pharmacokinetics of ramipril and ramiprilat were investigated on day 4. Effects on plasma renin activity, ACE activity, and heart rate and blood pressure both before and after a standardized exercise test were measured on days 1 and 4. On day 4 the combination reduced the mean arterial pressure by 2.8 mmHg compared with propranolol alone and by 3.7 mmHg compared with ramipril alone. Ramipril had no effect on the bradycardia induced by propranolol. Propranolol reduced exercise mean arterial pressure by 9 mmHg (day 4) and heart rate by 7 beats.min-1 (day 4) compared with ramipril; this was not affected by co-administration of ramipril. On day 4 the average plasma renin activity was not significantly higher than after the combination. ACE activity was not affected by propranolol. The pharmacokinetics of ramipril and ramiprilat were not influenced by propranolol. The combination of ramipril and propranolol has additive pharmacodynamic effects that may be useful in the treatment of hypertension.

Administration, Oral↗
PubMed1993

Counterregulatory hormone responses during graded hyperinsulinemic euglycemia in conscious rats.

It has been suggested that hyperinsulinemia per se may affect the levels of some counterregulatory hormones in the absence of hypoglycemia. We studied the effect of graded hyperinsulinemia and concomitant increased glucose metabolism on the levels of counterregulatory hormones by means of the 5-step sequential hyperinsulinemic euglycemic clamp technique, combined with [3-3H]-glucose infusion, in conscious rats. Insulin infusion rates (IIR) of 0, 0.5, 1, 3, and 16 mU/min, resulted in steady-state plasma insulin levels (mean +/- SEM) of 24 +/- 4, 44 +/- 3, 98 +/- 8, 418 +/- 48, and 6626 +/- 361 microU/ml, peripheral glucose uptake (PGU) of 3.1 +/- 0.2, 3.6 +/- 0.3, 5.4 +/- 0.3, 9.2 +/- 0.4, and 12.4 +/- 0.2 mg/min and hepatic glucose production (HGP) of 3.1 +/- 0.2, 2.4 +/- 0.4, 0.8 +/- 0.3, -0.1 +/- 0.2, and -0.5 +/- 0.3 mg/min, respectively. Plasma glucagon levels were half maximally suppressed between IIRs of 0.5 and 1 mU/min and maximally suppressed at 3 mU/min. The suppression exactly paralleled the inhibition of HGP (r = 0.87 +/- 0.04, p < 0.02) but not the stimulation of PGU (r = -0.66 +/- 0.12, p = NS). This suggests that the inhibition of HGP by insulin is at least partially mediated by a simultaneous suppression of plasma glucagon levels. The adrenal hormones corticosterone and epinephrine were not influenced during the clamp.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Chronic stimulation of atrial natriuretic peptide attenuates the secretory response to postural changes.

Atrial natriuretic peptide (ANP), released upon pulmonary vasoconstriction, modulates pulmonary vascular tone through an increase of cellular guanosine 3',5'-cyclic monophosphate. In patients with cardiopulmonary disease, however, the plasma levels of ANP are relatively low, considering the high pulmonary arterial pressure. To evaluate the release mechanism of the hormone, plasma ANP levels were studied by the manipulation of right atrial stretch with different body postures. In healthy young subjects, the plasma ANP concentration significantly increased when posture changed from an upright to a supine position (p < 0.01). In contrast, plasma ANP concentrations were significantly higher in patients with chronic obstructive pulmonary disease and elderly subjects (p < 0.01), but the plasma levels did not increase upon the change in posture. Consistent with in vitro findings, the data indicate that chronic ANP stimulation attenuates the secretory response to acute stimuli. In addition, it was demonstrated that the ratio of guanosine 3',5'-cyclic monophosphate to ANP, reflecting the biologic effect of the hormone, was significantly lower in patients with chronic obstructive pulmonary disease as well as in the elderly (p < 0.05). This decreased biologic activity aggravated the blunted ANP response and may contribute to the development of pulmonary hypertension.

Adult↗
PubMed1993

Weight changes in critically ill patients evaluated by fluid balances and impedance measurements.

OBJECTIVE: To study simple, rapid, and predictive methods to determine body weight changes in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Thirty-one consecutive patients. INTERVENTIONS: Calculated weight changes, using day-to-day and cumulative fluid balances corrected (in two ways) for insensible losses, were compared with the actual weight changes (mattress bascule). A tetrapolar impedance technique measuring resistance was evaluated for estimating weight changes. MEASUREMENTS AND MAIN RESULTS: No reliable relationship was found between calculated weight changes using fluid balances corrected for insensible loss and the observed weight changes. An intraindividual relationship was found between actual weight changes and changes in resistance measured with the tetrapolar impedance technique in a group of 24 critically ill patients with large weight changes (11.1 +/- 6.7 kg). No such intraindividual relationship was found in seven patients with small weight changes (3.1 +/- 2.2 kg). In each patient, the slope coefficient of the change in weight and resistance relationship differed; this individual slope coefficient could be an indication for hydration. CONCLUSIONS: Calculated fluid balances are not predictive for actual weight changes in critically ill patients. Absolute weight measurements are indispensable. Changes in resistance correlated with weight changes in individual patients if weight changes were > 3 kg.

Adolescent↗
PubMed1993

Islet cell hormone release immediately after human pancreatic transplantation. A marker of tissue damage associated with cold ischemia.

Pancreatic graft procurement, preservation, and transplantation surgery may result in damage to and loss of the integrity of endocrine cells and consequently in leakage of cell products into the insular vascular capillaries. Thus, the amount of alpha-, beta-, and pancreatic polypeptide (PP) cell products released into the vascular space of the recipient immediately after graft reperfusion may reflect islet cell injury. To test this hypothesis, we assessed glucagon, PP, C-peptide, and insulin levels in a prospective study of 22 consecutive renal-pancreatic transplantations. Transplantation-related parameters were used to account for differences in hormone release. Five grafts were preserved using Euro-Collins preservation fluid and 17 grafts were preserved using University of Wisconsin solution (UW). The first sign of a reinstalled physiological axis was the decrease of the blood glucose concentration after a median duration of 40 min (range 5-90 min) and the association of the recipient's ambient blood glucose levels with insulin release between 25 and 180 min after reperfusion. The delay period before a fall in blood glucose was observed correlated with cold ischemia time (rs = 0.73, P < 0.001, n = 21). An immediate and marked increase in plasma levels of glucagon (from 180 +/- 18 to 585 +/- 99 ng/L, mean +/- SEM), PP (from 57 +/- 8 to 122 +/- 13 pmol/L), C-peptide (from < 0.06 +/- 0.02 to 5.43 +/- 0.63 nmol/L), and insulin (from 0.15 +/- 0.21 to 2.05 +/- 0.26 nmol/L) was observed. C-peptide release correlated with glucagon (r = 0.76, P < 0.001) and PP (r = 0.60, P < 0.01). The hormone release was compared with computed tomography scans that were performed in the immediate postoperative period in 15 UW-preserved allografts. The diameter of the pancreatic head was increased and ranged from 4.5 to 7.7 cm (mean 6.2 cm). Peroperative C-peptide release significantly correlated with morphological graft changes reflected by the pancreatic head diameter (r = 0.58, P = 0.02). In a stepwise multiple regression analysis, cold ischemia time was a significant factor for the release of PP (r2 = 0.18, P = 0.049) and C-peptide (r2 = 0.35, P = 0.004). We suggest that peroperative hormone release reflects endocrine tissue damage. Furthermore, cold ischemia time may jeopardize the pancreatic allograft after relatively short preservation times, even when UW is used.

Adult↗
PubMed1993

Effects of hypoxia and atrial natriuretic peptide on aldosterone secretion in healthy subjects.

To evaluate the inhibitory effect of hypoxia and atrial natriuretic peptide (ANP) on aldosterone secretion, 11 healthy male subjects were infused with 5 ng.kg-1 x min-1 ANP or placebo. The subjects were exposed in a stepwise fashion to incremental hypobaric hypoxia, which decreased arterial oxygen saturation to 79 +/- 2% in the placebo and 84 +/- 2% in the ANP condition (P < 0.05). In the placebo condition, the plasma ANP concentration increased from 13.8 +/- 1.0 to 19.6 +/- 2.3 pmol/l (P < 0.01) at the lowest barometric pressure. Plasma renin activity did not change, whereas the plasma aldosterone levels increased consequent to the increase of plasma adrenocorticotropic hormone (ACTH). Continuous infusion of ANP increased the plasma levels twofold (P < 0.001) and the level of guanosine 3',5'-cyclic monophosphate threefold (P < 0.001). However, the plasma aldosterone concentrations were not different in the two experimental conditions. Administration of supplementary oxygen significantly decreased ACTH to baseline values (P < 0.01) together with a decrease in aldosterone. Free water clearance (P = 0.05) but not sodium excretion (P = NS) increased during continuous ANP infusion. The data indicate that the aldosterone secretion in hypoxia is not inhibited by (patho)physiological plasma ANP levels. The inhibition of aldosterone secretion may well be explained by a direct effect of hypoxia on the adrenal cells. ACTH is a major stimulus of aldosterone secretion in hypoxia, which overrides the natriuretic effect of ANP.

Adrenocorticotropic Hormone↗
PubMed1993

Alterations in calcium metabolism in young people at risk for primary hypertension. The Dutch Hypertension and Offspring Study.

Several disturbances in calcium metabolism have been reported in primary hypertensive subjects. It is, however, not clear whether these alterations predate the development of hypertension or occur as a consequence of high blood pressure. We studied indexes of calcium metabolism in three groups of normotensive children with different familial predispositions for hypertension, based on parental blood pressure levels, with two, one, or no hypertensive parents. Plasma intact parathyroid hormone [1-84] was higher in the offspring of hypertensive parents compared with offspring of normotensive parents (difference, 0.58 pmol/L; standard error of the difference [SED], 0.24; p = 0.02). Mean serum calcium levels were slightly reduced in the offspring of two hypertensive parents (-0.019 mmol/L, SED = 0.013, p = 0.17). Plasma magnesium and phosphate levels were lower in the offspring of hypertensive parents (-0.032 mmol/L [SED = 0.016, p = 0.05] and -0.045 mmol/L [SED = 0.024, p = 0.05], respectively). Mean 1.25-dihydroxyvitamin D3 levels were similar among the groups. No differences in dietary intake of calcium, phosphate, or fiber were found. Urinary calcium excretion per 24 hours and the ratio of 24-hour urinary calcium excretion to daily calcium intake were somewhat higher in the offspring of hypertensive parents. Renal fractional excretion of calcium was similar in the offspring of two hypertensive parents, and renal fractional excretion of phosphate was lower in the offspring of two hypertensive parents compared with offspring of two normotensive parents (-1.50%, SED = 0.74, p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Atrial natriuretic peptide improves pulmonary gas exchange in subjects exposed to hypoxia.

Atrial Natriuretic Peptide (ANP) is secreted in response to hypoxia and pulmonary vasoconstriction. The hormone modulates pulmonary vascular tone in vivo and decreases pulmonary edema in isolated lungs exposed to several toxic agents. In addition, ANP improves the barrier function of endothelial cell monolayers in vitro. The plasma levels of ANP are elevated in patients with high-altitude pulmonary edema. We hypothesized that under these circumstances, ANP improves pulmonary gas exchange by attenuating the transvascular permeation of plasma (water). Therefore, we studied the effect of low-dose ANP in 11 healthy mountaineers exposed to hypoxia in a single-blind, placebo-controlled, cross-over design. During four 1-h periods, the subjects were stepwise exposed to decreasing barometric pressure, with a minimum of 456 mm Hg (simulated altitude, 4,115 m). Infusion of 5 ng/kg/min human-ANP increased the plasma ANP concentrations approximately twofold. The plasma concentrations of cyclic GMP, which is the second messenger of ANP, rose approximately threefold. Infusion of ANP did not affect the hemodynamic or ventilatory response to hypoxia. The hemoglobin concentration, however, rose from 9.0 +/- 0.1 to 9.4 +/- 0.1 mmol/L (p < 0.01) during ANP infusion but not during placebo infusion. The change in plasma volume calculated from this hemoconcentration indicated that approximately 10% of the plasma volume had permeated into the interstitium. Despite the observed whole-body hemoconcentration, oxygen saturation was significantly higher during ANP infusion than during placebo infusion (84.7 +/- 1.7 versus 79.6 +/- 1.8%, p < 0.05), and the alveolar-arterial oxygen difference was significantly lower (3.5 +/- 0.7 versus 7.3 +/- 0.8 mm Hg, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin.

We have investigated ACTH and cortisol secretion patterns in two groups of five healthy adult male and female subjects. Plasma samples were obtained at 10-min intervals for 24 h, and pulsatile hormone release was analyzed by a multiparameter deconvolution technique. ACTH secretion was greater in male than female subjects; the production rate per 24 h was 139 +/- 7 pmol/L distribution volume in males, and 89 +/- 11 pmol/L distribution volume in females (P = 0.007). Cortisol secretion did not differ significantly between sexes; in males, the 24-h secretion rate was 2807 +/- 239 nmol/L distribution volume, and in females, it was 2970 +/- 411 nmol/L distribution volume (P = NS). The number of ACTH secretory pulses per 24 h, as determined by deconvolution analysis, was 16.2 +/- 1.4 in males and 19.6 +/- 2.0 in females (P = NS). There were no sex differences in the number of cortisol pulses or the calculated half-lives of ACTH and cortisol. ACTH and cortisol pulses were significantly concordant at a cortisol lag time of 10 min, as demonstrated by probability analysis and cross-correlation with auto-regressive modeling. Based on a significantly different regression intercept of cortisol pulse height on ACTH pulse height in women than in men (P < 0.001) and a higher ratio of cortisol to ACTH production rates in women than in men (P = 0.013), we suggest that the female adrenal cortex is more responsive to ACTH than its male counterpart in terms of glucocorticoid production. Consequently, equivalent daily cortisol secretion rates are attained in men and women at the expense of greater ACTH release in men.

Adrenocorticotropic Hormone↗
PubMed1993

The influence of serotonergic neurotransmission on pituitary hormone release in obese and non-obese females.

It has been suggested that a defect in hypothalamic serotonergic neurotransmission may be partly responsible for the impaired pituitary hormone release in obese subjects. In this study we investigated basal serum pituitary hormone concentrations and pituitary hormone release in response to the sequential injection of four hypothalamic releasing hormones before and after a seven-day course of fluoxetine, which inhibits serotonin re-uptake by presynaptic neurons and acts specifically in the brain. Ten obese women (body mass index (BMI) 35.6 +/- 1.0 kg/m2) and nine women of normal weight (BMI 22.9 +/- 0.9 kg/m2) were studied in the early and mid-follicular phases of the menstrual cycle. Basal concentrations of pituitary hormones were measured at 09.00. Subsequently 200 micrograms of TRH and 100 micrograms of CRH, GnRH and GHRH were injected intravenously. The pituitary hormone response was measured at regular intervals until 180 min after the four injections. The experiment was repeated after a seven-day course of 60 mg fluoxetine orally. We found the basal concentrations of prolactin (PRL) and growth hormone to be significantly lower in obese subjects than in the normal controls. Basal concentrations of ACTH, beta-endorphin, TSH, LH and FSH in the two groups were comparable. Releasing hormone-induced responses in the two groups were not significantly different. Administration of fluoxetine "restored" the basal PRL concentrations in obese subjects. It did not affect the other basal hormone concentrations. Furthermore, fluoxetine treatment reduced TRH-induced TSH release in both normal and obese subjects. It did not influence the other releasing hormone-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1993

Evidence for brain serotonin-mediated control of carbohydrate consumption in normal weight and obese humans.

A plasma insulin and amino acid-mediated mechanism is thought to modulate brain serotonin concentration, thereby regulating carbohydrate consumption on a meal to meal basis. It has been suggested that obesity is associated with a defect in the appetite control system. Furthermore, post-absorptive plasma levels of several amino acids are increased in obese subjects, which is ascribed to obesity-associated insulin resistance and/or hyperinsulinemia. We studied breakfast-induced changes in plasma ratios of tryptophan to other large neutral amino acids and associated differences in macro-nutrient composition of lunch food in normal weight and obese human subjects. The study was randomized, double blind and cross-over with a 2 x 2 factorial design with drug/placebo and type of breakfast as factors. Nineteen healthy, non-obese (body mass index (BMI) 22.5 +/- 1.9 kg/m2, mean +/- s.d.) and 19 obese (BMI 34.7 +/- 6.2 kg/m2) female volunteers were treated with either 60 mg fluoxetine (FXT), a serotonin re-uptake blocker specifically acting in the brain, or placebo for four days with a wash-out period between treatments of four weeks. The subjects received either a carbohydrate (CHO) breakfast (80 g maltodextrin, 300 kcal) or a protein-rich (PROT) breakfast (60% milk protein and 40% CHO, 300 kcal) on two consecutive days (days 4 and 5 of each treatment period). Plasma glucose, insulin and amino acids were measured at several time points after breakfast. Three hours after breakfast, subjects were able to choose from 29 different food items. Total energy content and weight of lunch food and energy percentage of each macronutrient were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

In vivo insulin responsiveness for glucose uptake and production at eu- and hyperglycemic levels in normal and diabetic rats.

UNLABELLED: Whole body glucose uptake (BGU) and hepatic glucose production (HGP) at maximal plasma insulin concentrations (+/- 5000 microU/ml) were determined by eu- (EC) (6 mM) and hyperglycemic (HC) (20 mM) clamps (120 min), combined with [3-3H]glucose infusion, in normal and streptozotocin-treated (65 mg/kg) 3-day diabetic, conscious rats. In normal rats, during EC, BGU was 12.4 +/- 0.4 mg/min and during HC, when urinary glucose loss was 0.54 +/- 0.09 mg/min, BGU was 25.5 +/- 1.6 mg/min. However, throughout the final 60 min of HC, glucose infusion rate (GIR) was not constant but a linear decline in time (r = -0.99) of 17%, P less than 0.0001, was observed indicating a hyperglycemia-induced desensitization process. In diabetic rats, during EC, BGU was 7.7 +/- 0.3 mg/min and during HC, BGU was 15.5 +/- 1.4 mg/min. Throughout the final 60 min of HC, GIR was constant, suggesting that the hyperglycemia-induced desensitization process was already completed. In normal and diabetic rats, HGP was similar: during EC 0.2 +/- 0.5 mg/min and 0.1 +/- 0.5 mg/min, and during HC 0.4 +/- 0.4 mg/min and 0.5 +/- 0.6 mg/min, respectively. In vitro adipocyte and muscle insulin receptor studies showed normal to increased receptor number and increased receptor autophosphorylation in diabetic compared to normal rats. IN CONCLUSION: (i) 3-day diabetic rats show, at maximal plasma insulin concentrations, insulin resistance to BGU, but not to HGP. The resistance to BGU is equally present (reduction of 38%) at eu- and hyperglycemic levels as compared to normal rats. (ii) 3-day diabetic rats reveal no defect in adipocyte and muscle insulin receptor function. These data indicate that the diabetes induced insulin resistance for BGU is at the post-receptor level and due to a decreased maximal capacity (Vmax) for glucose uptake, with no change in affinity, or Km.

Adipose Tissue↗