Search PubMed⌕ Search

Biomedical subjects

M Frölich

Publications and source records attributed to M Frölich.

At least 91 records · Page 5Linked to original sources
PubMed1996

Cerebral vasoconstriction in comatose patients resuscitated from a cardiac arrest?

OBJECTIVE: To determine the role of cerebral vasoconstriction in the delayed hypoperfusion phase in comatose patients after cardiac arrest. DESIGN: Prospective study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: 10 comatose patients (Glasgow Coma Score +/- 6)successfully resuscitated from a cardiac arrest occurring outside the hospital. MEASUREMENTS: We measured the pulsatility index (PI) and mean blood flow velocity (MFV) of the middle cerebral artery, the cerebral oxygen extraction ratio and jugular bulb levels of endothelin, nitrate, and cGMP during the first 24 h after cardiac arrest. RESULTS: The PI decreased significantly from 1.86 +/- 1.02 to 1.05 +/- 0.22 (p = 0.03). The MFV increased significantly from 29 +/- 10 to 62 +/- 25 cm/s (p = 0.003). Cerebral oxygen extraction ratio decreased also from 0.39 +/- 0.13 to 0.24 +/- 0.11 (p = 0.015). Endothelin levels were high but did not change during the study period. Nitrate levels varied widely and showed a slight but significant decrease from 37.1 mumol/l (median; 25th-75th percentiles: 26.8-61.6) to 31.3 mumol/l (22.1-39.6) (p = 0.04). Cyclic guanosine monophosphate levels increased significantly from 2.95 mumol/l (median; 25th-75th percentiles: 2.48-5.43) to 7.5 mumol/l (6.20-14.0) (p = 0.02). CONCLUSIONS: We found evidence of increased cerebrovascular resistance during the first 24 h after cardiac arrest with persistent high endothelin levels, gradually decreasing nitrate levels, and gradually increasing cGMP levels, This suggests that active cerebral vasoconstriction due to an imbalance between local vasodilators and vasoconstrictors plays a role in the delayed hypoperfusion phase.

Adult↗
PubMed1996

Recurrent hypoglycaemia caused by the insulin autoimmune syndrome: the first Dutch case.

The insulin autoimmune syndrome is extremely rare outside of Japan. We describe a 45-year-old Caucasian woman who presented with fasting hypoglycaemia and weight gain. The presence of fasting insulin concentrations in excess of 1000 mU/l, very low C-peptide concentrations during hypoglycaemic attacks and high titres of insulin autoantibodies led to the diagnosis. Treatments aimed at decreasing endogenous insulin secretion by either dietary intervention alone or in combination with acarbose, octreotide or diazoxide had only limited success, while a 2-week course of immunosuppression with prednisone was without any antihypoglycaemic effect.

Autoantibodies↗
PubMed1996

Specific stimulation of brain serotonin mediated neurotransmission by dexfenfluramine does not restore growth hormone responsiveness in obese women.

OBJECTIVE: Growth hormone release in response to all known stimuli of GH secretion is blunted in obese subjects. Several studies, using d,l-fenfluramine (d,l-FF) as a serotoninergic tool, suggest that brain serotonin plays a role in the pathogenesis of this phenomenon. However, the effect of d,l-FF appears to be dependent on the stimulus used to induce GH release. Furthermore, d,l-FF has catecholamingergic properties apart from its capacity to stimulate serotonin release and to block its re-uptake. In this study, we investigated whether subchronic treatment with the highly selective serotoninergic drug dexfenfluramine (d-FF) affects the GH response to galanin or GHRH in obese subjects. DESIGN: The study had a randomized, cross-over, placebo controlled design. d-FF was administered in a dose of 15 mg twice daily during 6 days. On days 5 and 6 of treatment (with either d-FF or placebo) an i.v. bolus injection of 100 micrograms hGHRH(1-44) or a continuous infusion of p-galanin (40 pmol/kg/min over 40 minutes) were administered in randomized order. All tests were performed in the follicular phase of two consecutive menstrual cycles. PATIENTS: Eight obese women (body mass index (BMI) 34.5 +/- 3.6 kg/m2); 7 normal weight (BMI 21.9 +/- 1.9 kg/m2) age-matched control women. All women had a regular menstrual cycle. None used oral contraceptive drugs. MEASUREMENTS: GH response to either stimulus was measured both during treatment with d-FF and during treatment with placebo. RESULTS: The GH response to galanin and the response to GHRH were significantly smaller in obese subjects. d-FF significantly reduced the galanin induced GH secretion in obese subjects, but not in normal weight controls. It did not significantly affect GH release in response to GHRH in either group. CONCLUSION: This study confirms that GH secretion in response to stimuli with varying mechanisms of action is blunted in obese subjects. A decrease of central serotonin mediated neurotransmission does not appear to play a role in the pathogenesis of this phenomenon.

Adult↗
PubMed1996

Prediction of the outcome of treatment of Paget's disease of bone with bisphosphonates from short-term changes in the rate of bone resorption.

In Paget's disease of bone, bisphosphonate therapy is usually given for 3-6 months, at which point the success of treatment is assessed by measuring serum alkaline phosphatase activity. The changes, however, in bone resorption and formation after bisphosphonate therapy are predictable, and their correct interpretation may allow a rational therapeutic approach applicable to the individual patient. We addressed this issue in 21 patients with active Paget's disease treated with 2 different nitrogen-containing bisphosphonates for 10 days. Urine samples were collected daily before and during treatment for the measurement of the following collagen degradation products, as indexes of bone resorption; cross-linked N-telopeptide of collagen type I (NTx), free deoxypyridinoline with 2 different assays, and hydroxyproline. Independently of the structure of the bisphosphonate used, the magnitude of decrease in urinary NTx with treatment was greater than that of both deoxypyridinoline assays and practically identical to the decrease in excess of urinary hydroxyproline. The degree of suppression of NTx on the 9th and 10th days of treatment correlated with the lowest serum alkaline phosphatase activity obtained during 1 yr of follow-up. All patients in whom serum alkaline phosphatase activity normalized during follow-up showed a suppression of NTx greater than 75% of the initial values after 10 days of treatment. We conclude that urinary NTx is a sensitive and specific index to follow the efficacy of bisphosphonate therapy in patients with Paget's disease and that measurements of its values before and after a short period of treatment can provide a simple and convenient way to predict the final therapeutic outcome and to avoid unnecessary continuation of treatment in many patients with Paget's disease of bone.

Adult↗
PubMed1996

An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women.

Although many studies have discerned higher serum GH concentrations in women than in men, based on measurements of single random blood samples or integrated 24-h means, the neuroendocrine mechanisms that underlie such gender differences have not been defined. Such mechanisms might entail an increase in GH-secretory burst frequency, amplitude, or duration, heightened interpulse basal GH release, or a prolonged half-life of GH. These mechanisms can be distinguished by deconvolution analysis of appropriate GH time series. Earlier studies employed RIA or IRMA with sensitivities of 0.1-0.5 microgram/L, which result in frequently undetectable serum GH concentrations. To address these limitations, we undertook blood sampling at 10-min intervals for 24 h and applied a high-sensitivity immunofluorometric assay of GH (sensitivity 0.0115 microgram/L). Multiparameter deconvolution analysis was used to estimate specific features of GH secretion, while simultaneously calculating the half-life of endogenous GH. Eleven men and 11 premenopausal women from the same community were studied. Discrete peak detection by Cluster was employed as a complementary half-life-independent technique to assign variations in serum GH into pulsatile and basal fractions over 24 h. Cluster revealed significantly higher mean serum GH concentrations over 24 h in women (0.78 +/- 0.08 microgram/L) compared with in men (0.27 +/- 0.03 microgram/L, P < 0.00005). Women exhibited significantly higher maximal serum GH concentration peak values than men (2.08 +/- 0.34 microgram/L in women, 0.67 +/- 0.11 microgram/L in men, P = 0.0008), which could be, in turn, attributed to a significantly increased incremental serum GH peak amplitude (1.85 +/- 0.33 microgram/L in women vs. 0.60 +/- 0.10 microgram/L in men, P = 0.0021) and a longer peak duration (114 +/- 8 min in women, 86 +/- 4 min in men, P = 0.008). The mean area under the serum GH concentration peak was significantly (3-fold) higher in women than in men (98 +/- 17 micrograms/L.min in women, 34 +/- 8 micrograms/L.min in men, P = 0.0046). Serum GH peak frequency was similar in women (9.7 +/- 0.8 peak/24 h) and men (10.7 +/- 1.1 peak/24 h, P = NS). The mechanisms underlying the increase in serum GH concentration pulse amplitude, duration, and area were investigated further by deconvolution analysis. Deconvolution analysis disclosed equivalent secretory pulse frequencies in women and men (13 +/- 0.9 bursts/day in women, 10.5 +/- 1.3 bursts/day in men,P = NS), and statistically indistinguishable mean interburst intervals of 106 +/- 8 min in women and 150 +/- 26 min in men (P = NS). GH-secretory burst mass was significantly higher in women by approximately 2.4-fold (P = 0.0013) compared with in men, which was attributed to a greater burst amplitude. Only low levels of basal GH release were inferred in women (5%) and men (9%), which did not differ significantly between genders. Moreover, the calculated half-life of endogenous GH was no different in women compared with in men: 15.8 +/- 0.7 min vs. 17.1 +/- 0.8 min, respectively (P = NS). The calculated daily secretion rate was 3-fold higher in women (47 +/- 4.8 micrograms/L.24 h) than in men (15 +/- 1.8 micrograms/L.24 h) (P < 0.001). In summary, discrete peak-detection analysis of serum GH concentration profiles collected at 10-min intervals over 24 h in men and premenopausal women discloses significantly different mean serum GH concentrations that are accounted for by higher maximal and incremental serum GH peak amplitudes. Deconvolution analysis demonstrated that the mechanism supporting the amplitude-specific difference in women was an augmentation of the GH-secretory burst mass caused by a higher GH-secretory burst amplitude. These gender differences were highly specific because the frequency of detectable GH-secretory bursts, the calculated endogenous half-life, and the estimated basal GH release were no different in women than in men.

Adolescent↗
PubMed1995

Insulinotropic effects of cholecystokinin, gastric inhibitory polypeptide and glucagon-like peptide-1 during perifusion of short-term cultured canine isolated islets.

Recent metabolic studies suggest that the incretin effect of gut hormones may account for most of the circulating insulin during mild postprandial hyperglycemia after transplantation of isolated islets. As yet, however, insulinotropic effects of pharmacological rather than physiological levels of the incretin candidates cholecystokinin-33 (CCK-33), gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1) on isolated perifused islets have been reported. We examined the insulinotropic effects of these peptides during perifusion of canine isolated islets. Exploration of beta-cell sensitivity in our model with graded 0.1-10 nM doses of CCK-33 and GIP at a 7.5 mM glucose level demonstrated insulinotropic effects from the lowest level. We, therefore, focused on the (near-) physiological effects of both CCK-33 (20 pM), GIP (500 pM), and GLP-1 (100 pM) during perifusion at a 2.5, 7.5, and 10 mM glucose level. No effects of CCK-33 were observed. GIP enhanced insulin release 1.1- and 1.2-fold, at the 7.5 and 10 mM glucose level, respectively. GLP-1 stimulated insulin output from the 2.5 mM glucose level; and a maximum, 2-fold, increase of insulin output was observed from the 7.5 mM glucose level. Thus, isolated perifused islets do respond to near-physiological beta-cell stimulation with gut hormones, and both GIP and GLP-1 may contribute to a hyperglycemia-enhanced activation of the enteroinsular axis after transplantation of isolated islets.

Animals↗
PubMed1995

Plasma amino acid ratios related to brain serotonin synthesis in response to food intake in bulimia nervosa.

Fifteen bulimic women (BN) and 19 healthy female controls (CO) were studied. The subjects were cross-over treated with either fluoxetine (FXT) or placebo during 4 days. They received, in randomized order, a breakfast containing pure carbohydrate (CHO) or a protein-rich (PROT) breakfast following day 3 and 4 of each treatment period. Twenty-nine different food items were offered for lunch. The fasting serum glucose and insulin concentrations and the fasting plasma tryptophan (Trp)/large neutral amino acid (LNAA) ratio were slightly higher in BN. The changes of these metabolic parameters in response to a CHO or PROT breakfast were similar in both groups. Across breakfast type, the plasma (Trp)/(LNAA) ratio at 120 min after breakfast was higher in BN. Total caloric intake at lunchtime was less in BN. In CO, less carbohydrate was selected at lunchtime following the CHO breakfast, an effect that was abolished by FXT. Breakfast type or FXT did not have any apparent effect on food intake at lunchtime in BN. This might indicate that bulimic subjects are less sensitive to serotoninergic stimuli than control subjects.

Adult↗
PubMed1995

Predictive value of tetrapolar body impedance measurements for hydration status in critically ill patients.

OBJECTIVE: To design and evaluate a simple and rapid method to predict body hydration status in critically ill patients. DESIGN: Prospective, consecutive sample. SETTING: Medical intensive care unit of a university hospital. PATIENTS: 31 consecutive patients. METHODS: All patients were classified daily for hydration status by the attending physician based on clinical impression, weight changes and laboratory measurements. The hydration status was scored as 'dehydrated', 'euvolemic' or 'edematous'. The total body impedance was measured daily by a tetrapolar impedance technique. RESULTS: Resistances > 700 omega were found in dehydrated subjects and resistances of < 400 omega in edematous patients. Weight gain was observed in dehydrated and weight loss in edematous patients. A discriminant analysis was used to create a predictive model for hydration using the daily impedance and weight measurements. If a cutoff point of 60% for the predicted classification was used to categorize the patient's hydration as dehydrated, euvolemic and edematous, no false positive predictions were observed for the dehydrated or the edematous state. CONCLUSION: Impedance measurements are in close agreement with the clinical impression of hydration of critically ill patients. Future investigations must elucidate the clinical importance.

Adolescent↗
PubMed1995

Stress, serotonergic function, and mood in users of oral contraceptives.

The relationship between stress and changes in insulin levels, plasma ratio of tryptophan to other large neutral amino acids (LNAAs), mood, and food intake was investigated in women taking monophasic oral contraceptives containing progestagens. Subjects experiencing high levels of stress displayed significant decreases of insulin and tryptophan to other LNAAs ratios, before and after the consumption of a standard meal during the pill-free period as compared with the period of pill use. The decline of the tryptophan to other LNAAs ratio was accompanied by worsening of mood. In a control group of subjects experiencing low levels of stress there was no relationship between insulin and tryptophan to other LNAAs ratio, nor between tryptophan to other LNAAs ratio and mood. These results suggest that the combination of stress and alterations in sex hormones may be responsible for mood changes during the pill-free period in women taking oral contraceptives.

Adult↗
PubMed1995

Combining salicylate and enalapril in patients with coronary artery disease and heart failure.

OBJECTIVE: To study the effects of adding a salicylate to the angiotensin converting enzyme inhibitor enalapril in patients with heart failure due to coronary artery disease. DESIGN: Double blind, crossover study for three days in hospital followed by an extended similar study outside hospital over two months of once daily enalapril plus salicylate and enalapril plus placebo. SETTING: Tertiary referral centre. PATIENTS: 20 patients with heart failure due to myocardial infarction (New York Heart Association class II or III) and an ejection fraction less than 0.40. Twelve patients completed the two parts of the study. MAIN OUTCOME MEASURES: Blood pressure, plasma converting enzyme activity; plasma angiotensin II and noradrenaline concentrations; excretion of metabolites of renal and systemic prostanoids. RESULTS: The unloading effect of first and second dose of enalapril in the morning lasted only during the day; in the extended study it lasted 24 hours because of the drug's accumulation. Converting enzyme inhibitors attenuate the breakdown of bradykinin and therefore enhance prostaglandin E2 synthesis mediated by bradykinin. Evidence was found of such a prostaglandin E2 mediated contribution to ventricular unloading by enalapril, which was blocked by salicylate. The contribution, however, was small and variable, and salicylate addition had on average no significant de-unloading effect during the day. Unloading was abolished in only three of the 20 patients in the short term study and in one of the 12 in the extended study. At night, when other effects of enalapril on blood pressure had waned and the bradykinin induced effect persisted, salicylate significantly reduced the remaining small unloading effect. No effect was seen of salicylate addition on reversal of remodelling. Enalapril reduced angiotensin II induced synthesis of systemic and renal prostaglandin I2 and thromboxane A2, initially only during the day, but later also at night. It thereby masked suppression of thromboxane A2 synthesis by salicylate, which is the effect to which reinfarct prevention by salicylate is attributed. CONCLUSION: The risk is low that salicylate will substantially reduce the benefit of enalapril in patients with heart failure by de-unloading the ventricle. Like other effects induced by bradykinin significant de-unloading occurs in only a minority of the patients. In the presence of enalapril, however, salicylate will probably not be as effective as expected in reducing reinfarction risk, because enalapril already reduces thromboxane A2 synthesis effectively in patients with heart failure and no further reduction by salicylate was found.

Adult↗
PubMed1995

Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing's disease: evidence for decreased responsiveness of the adrenal glands.

We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 +/- 0.7 vs. 19.3 +/- 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 +/- 2 vs. 59 +/- 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 +/- 1.9 in controls and 11 +/- 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.

Adrenal Glands↗
PubMed1995

Recovery of serum calcium concentrations following acute hypocalcemia in patients with osteoporosis on long-term oral therapy with the bisphosphonate pamidronate.

Bisphosphonates, synthetic compounds that are taken up preferentially by the skeleton and that suppress bone resorption, are currently used in the management of patients with osteoporosis. Long-term uninterrupted administration of low oral doses is the preferred mode of treatment in current clinical trials with newer bisphosphonates. These compounds have, however, a long residence time in the skeleton, and there is no information about their long-term effects on blood calcium homeostasis. We examined the effect of long-term therapy with oral bisphosphonate on blood calcium homeostasis following an acute hypocalcemic stimulus. Twenty patients with vertebral osteoporosis (10 untreated controls and 10 treated with oral pamidronate, 150 mg/day for at least 5 yr) were given intravenous infusions of sodium EDTA, and the concentrations of calcium and PTH in blood were followed for 24 h. Serum calcium concentrations decreased similarly in both groups (maximum decrease 0.21 mmol/L and 0.22 mmol/L, respectively). The recovery of serum calcium concentrations was identical in both groups, and all patients had normal concentrations at 24 h. Plasma PTH increased to a peak of 17.3 +/- 2.5 pmol/L in the control group and to 17.0 +/- 3.1 pmol/L in the pamidronate-treated patients. During the whole study period, there was no difference in either the peak PTH response or in the recovery of plasma PTH values between the two groups. However, when only PTH responses between 60 min and 24 h were examined, there were differences between the two groups. Plasma PTH values, although strictly within the normal range, were significantly higher in the pamidronate-treated patients (P = 0.001). There were no differences in the calcemic responses during this period. Further, there were no detectable changes in immunoreactive PTH-related protein in either group after the EDTA infusions. In conclusion, our study showed that longterm therapy with oral pamidronate does not affect the calcemic response to an acute hypocalcemic stimulus in patients with osteoporosis.

Acute Disease↗
PubMed1995

Hypoxia-induced arterial endothelin does not influence peripheral vascular tone.

The effect of hypoxia (SpO2 80%) on the arteriovenous production of endothelin-1 (ET) in the forearm was investigated in six healthy volunteers. In eight other subjects the local vascular effects of a low physiologic dose of intra-arterially administered ET (0.5 pg/kg/min) was studied during normoxia. Forearm blood flow (FBF) was measured by venous occlusion plethysmography, and arterial and venous plasma concentrations of ET were measured. FBF was not significantly influenced during hypoxia. After 15 min of hypoxia the arterial plasma level of ET increased from 2.5 +/- 0.1 to 3.3 +/- 0.3 ng/L (p < 0.05), whereas the venous plasma level remained unchanged. Intra-arterial infusion of ET increased the arterial plasma level of ET in the forearm from 2.2 +/- 0.3 to 4.9 +/- 0.4 ng/L. This increase in ET concentration did not influence FBF. It is concluded that hypoxia is a stimulus for ET release from the pulmonary vascular bed and that the resulting increase arterial plasma ET level does not influence peripheral vascular tone.

Adult↗
PubMed1995

beta-Adrenergic receptors contribute to hypoxaemia induced vasodilation in man.

1. It was the aim of the present study to investigate the role of the beta-adrenergic receptor in hypoxaemia induced vasodilatation in the human forearm. 2. The study was performed in 12 non-smoking male volunteers. In six subjects the local vascular effects of intra-arterially (i.a.) infused propranolol (0.1 mu kg-1 min-1) was determined during normoxaemia and hypoxaemia (peripheral oxygen saturation; SpO2 80%), and compared with the contra-lateral (control) arm. beta-adrenergic receptor blockade by propranolol was confirmed by i.a. infusions of adrenaline. In six other subjects the effects of incremental hypoxaemia (SpO2 90, 85, 80%) on forearm- and finger blood flow was investigated. A difference between these vascular beds is the absence of vascular beta-adrenergic receptors in the finger. Forearm- and finger blood flow were measured by venous occlusion plethysmography. Plasma levels of (nor-)adrenaline were determined in both arterial and venous blood samples. Hypoxaemia was attained by gradual decompression of a hypobaric chamber and individually adjusted. 3. During normoxaemia the single infusion of propranolol did not influence forearm vascular resistance. In contrast, during hypoxaemia a net vasoconstriction was observed in the arm treated with propranolol, which was significantly different (P = 0.009) from the vasodilatation in the control arm (mean difference in response 40%; 95% confidence interval 13.2-66.8). The net arterio-venous spillover of noradrenaline from the forearm increased after the first 15 min of hypoxaemia (P < 0.05) and returned to baseline in the next 15 min. Arterial and venous plasma levels of adrenaline during hypoxaemia remained unchanged compared with normoxaemia. In the second set of experiments incremental levels of hypoxaemia induced a vasoconstriction in the finger, which was significantly different (P = 0.025) from the vasodilatation in the forearm (mean difference in response 300%; 95% confidence interval 63-537). 4. The data indicate that beta-adrenergic receptors contribute to hypoxaemia induced vasodilatation, despite unaltered adrenaline plasma concentrations.

Adult↗
PubMed1994

Impact of donor-related variables on islet isolation outcome in dogs.

Clinical human islet transplantation programmes are considerably hampered by the variability of islet isolation outcome. The effects of the islet content of the pancreas and other donor-related variables on isolation outcome have not been evaluated systematically so far--either in large animals, or in man. We studied the impact of interindividual differences in age, body weight and pancreatic islet content on the outcome of collagenase isolation of islets from the splenic pancreas of beagle dogs (n = 31). The islet volume of the splenic pancreas amounted to a mean (+/- SEM) 15.7 +/- 0.9 microliters per gramme pancreas, and varied three-fold (from 8.4 to 27.3 microliters). Isolated islet yield was 7.6 +/- 0.7 microliters/g and varied nine-fold (1.8-16.3 microliters). Animals also varied in age eight-fold (8-67 months) and body weight two-fold (8.6-18.3 kg). Differences in body weight and age explained 60% of variance in the fractional islet volume of the pancreas and 50% of the variance in islet yield (p < 0.001). Fractional islet volume of the splenic pancreas also explained 50% of the variance in islet yield (p < 0.001). We conclude that the outcome of islet isolation may be predictable after controlling for the variable islet content of pancreases, and other donor-related variables, and suggest that similar studies should be done in man.

Aging↗
PubMed1994

Insulin-induced decline of plasma amino acid concentrations in obese subjects with and without non-insulin-dependent diabetes.

Obesity-associated hyperaminoacidemia is traditionally interpreted as a consequence of insulin resistance. We performed two different experiments to investigate the effects of both obesity-associated insulin resistance and the insulin resistance of non-insulin-dependent diabetes mellitus (NIDDM) on amino acid metabolism. In the first experiment, we measured postabsorptive amino acid concentrations and their decline in response to an oral carbohydrate load in 19 obese nondiabetic women and 19 normal-weight nondiabetic controls. Obese subjects were more resistant to insulin with respect to its effects on glucose metabolism than normal-weight controls, as calculated by the method described by Matthews. However, postabsorptive plasma concentrations of the so-called large neutral amino acids (LNAA), namely phenylalanine, tyrosine, valine, leucine, and isoleucine, and their decrease in response to carbohydrate consumption were similar in both groups. In the second experiment, we compared the decrease of plasma concentrations of LNAA during a euglycemic, hyperinsulinemic clamp in obese subjects with and without NIDDM. Peripheral glucose uptake (PGU) was more impaired in NIDDM subjects compared with obese controls. Furthermore, hepatic glucose production (HGP) was less attenuated by insulin infusion in NIDDM than in control subjects. Postabsorptive plasma LNAA concentrations were not different in the two groups. Values obtained in either group were not different from the postabsorptive concentrations in the normal-weight control subjects of experiment 1. All amino acid levels decreased substantially in response to insulin infusion. The magnitude of the decrease was not significantly different in the two groups, except for a slightly greater decrease of the plasma isoleucine concentration in obese control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗