Enhanced glucose utilization during prolonged glucose clamp studies.
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Biomedical subjects
Publications and source records attributed to B Schulz.
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A subungual solitary glomus tumour was examined by both light and electron microscopy. By light microscopy, typical tumour tissue was seen, surrounded by connective tissue. By electron microscopy, a very close morphological relationship was noted between non-myelinated nerve fibres and mast cells. These mast cells could be divided into two groups: the mast cells of the first group contain numerous mature granules and show few lamellopodia. The distance to the nerve fibre bundles ranged between 2000 and 20 nm. In the second group, the mast cells always showed direct contact with nerve fibers. They had many lamellopodia and contained almost exclusively immature granules. In some cases, invaginations of lamellopodia and broader cytoplasmatic processes into the view that mast cells may play an important part in the function of neurons.
Pancreatic glucagon (IRG) and insulin (IRI) secretion patterns were studied in obese subjects with normal (n = 7), borderline (n = 5) and pathological carbohydrate tolerance (n = 11), as well as in 19 non-obese healthy controls without a family history of diabetes, by means of a 2-h glucose infusion (12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. With regard to the insulin secretion all obese groups were characterized by a significant hyperinsulinaemia during the late secretion phase, whereas the early insulin response ( delta IRI-area 0-5 min) was significantly reduced in obesity with pathological carbohydrate tolerance. There was no significant differences in fasting IRG levels among controls (29.7 +/- 6.1 pmol/l) and pathological glucose tolerance (31.2 +/- 4.6 pmol/l). In addition, absolute IRG levels and the IRG concentration pattern during glucose infusion were comparable in all groups confirming no alpha-cell resistance to glucose suppression in obesity, irrespective of normal or impaired carbohydrate tolerance. The molar IRI-IRG ratio was significantly increased during glucose infusion in all obese groups reflecting a relative anabolic state. There were no correlations between IRG secretion and relative body weight, glucose tolerance or insulin response to glucose.
We have studied changes in the sensitivity of the early insulin response to glucose by means of an intravenous pulse-stimulation of 1.0 g, 2.5 g and 5.0 glucose at intervals of 30 min in 24 non-obese healthy controls without a family history of diabetes and in obese subjects with normal (n = 7) and pathological carbohydrate tolerance (n = 23). All subjects were characterized regarding carbohydrate tolerance (CHT) by using a 2 h-glucose infusion test (GIT; 12 mg/kg/min), primed by an initial injection of 0.33 g/kg glucose. Compared with controls the early insulin response (delta IRI-area 0-5 min) during GIT was slightly increased in obesity with normal CHT and it was significantly reduced in obesity with pathological CHT. With regard to the late insulin response phase (delta IRI-area 30-120 min) both obese groups were characterized by a significant hyperinsulinemia. During staircase glucose stimulation a dose-dependent significant increase of the maximal IRI-response was observed in controls whereas this strong relationship was lacking in the two obese groups. The dose-response curve in obesity with normal CHT was displaced toward the left of the control curve whereas a right shift was found in obesity with pathological CHT. There was a significant correlation between early insulin response during GIT and maximal insulin response revealed by staircase glucose stimulation in obese subjects with pathological CHT. No close relationship of this type could be detected in the other groups so far studied. Our findings suggest an increased sensitivity of the beta-cells to glucose in the hyperinsulinemia stages of obesity with normal CHT. In contrast to this, a reduced sensitivity of the early insulin response to glucose is suggested in obesity with pathological CHT. A staircase glucose stimulation seems to be a useful tool in studying the early insulin response to glucose.
The importance of kidneys from newborn donors in transplantation has not been clearly defined. The purpose of this study was to investigate the degree of morphological and functional adaptation of the newborn kidney in an adult recipient. 7 MLS-matched kidneys from LEWE minipig puppies (age 3-4 weeks) had been transplanted en bloc to their mothers with immediately bilateral nephrectomy. Preliminary results suggested that arterial vasculature and blood supply are limiting factors in adaption of newborn donor kidneys in adult recipient.
The effect of a physical training and low caloric diet (700 calories/day) for 4 weeks on insulin sensitivity in vivo, body weight and serum lipids was investigated in 10 obese asymptomatic diabetics (normal fasting plasma glucose and pathological glucose tolerance). Glucose tolerance and insulin secretion pattern were characterized by means of a 2h-glucose infusion test (12 mg/kg/min) primed by an initial injection of 0.33 g/kg glucose. Insulin responsiveness in vivo was estimated by means of a 1h-insulin infusion test (two 30-min. periods of 8 and 16 mU/kg insulin MC-Actrapid, primed by initial injection of 1 and 2 mU/kg, respectively). Under comparable steady-state insulin levels the decrease in plasma glucose and free fatty acids (FFA) was considered as estimate of insulin sensitivity in vivo. Physical working capacity (PWC170) was determined by means of a bicycle ergometer test in stepwise working loads. The training programme consisted of daily 15 min. bicycle ergometer training periods (75% of the maximal working capacity) in the morning and a 1 h mild physical training on a bicycle in the afternoon. After the combined training and diet programme the mean decrease in absolute and relative body weight amounted to 11.9 +/- 1.07 kg and 16.7 +/- 1.2%, respectively. There was a significant decrease of plasma triglycerides whereas the decrease in cholesterol was modest. Physical fitness increased by delta PWC170 of 31.1 +/- 11.6 W. In addition, the combined training and diet programme for 4 weeks resulted in a significant improvement of insulin sensitivity in vivo as indicated by an augmented insulin-induced decrease in plasma glucose and FFA (17.60 +/- 3.91%, vs 36.40 +/- 5.54%; p less than 0.05 and 35.90 +/- 6.95% vs 56.50 +/- 3.63%; p less than 0.05; respectively). Our findings provide direct evidence that physical training and low caloric diet enhance insulin sensitivity in vivo. From the practical point of view our results suggest the potential benefits of physical training in the treatment of obese asymptomatic diabetics.
115 patients with normal weight and 15 adipose persons with suspicion of a disturbance of the carbohydrate metabolism were characterized by means of a glucose infusion test lasting two hours concerning the carbohydrate tolerance and insulin secretion. Longitudinal analyses of the spontaneous behaviour of the carbohydrate tolerance and insulin secretion depending on the degree of the carbohydrate tolerance up to duration of the observation of 7 years. A deterioration of the carbohydrate tolerance was to be proved in 21% of 87 persons with normal carbohydrate tolerance within two years. With normal carbohydrate tolerance within two years. With an increase of the duration of the observation up to 7 years the frequency of disturbances of the carbohydrate tolerance increases to 30%. This development cannot be coordinated to a certain type of insulin secretion. In the individual case a deterioration of the carbohydrate tolerance may be associated with an increase or reduction of the glucose stimulated insuline secretion. An improvement of the carbohydrate tolerance was observed in 15 (54%) of 28 patients with disturbed carbohydrate tolerance within 2 years. In a group with pathological carbohydrate tolerance this development was associated with a significant reduction of the basic and glucose stimulated insulin secretion. In all patients with improved carbohydrate tolerance on the side of the insulin secretion primarily the type of "normal response" was present. The lacking relation between changes of the B-cell function and the carbohydrate tolerance emphasizes the importance of other factors, such as a peripheral insulin resistance, for the development of disturbances in the carbohydrate metabolism.
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Twenty-three normal weight subjects without any heredity of diabetes were characterized by a 2-hour glucose infusion test. All persons showed a normal carbohydrate tolerance and normal biphasic insulin secretion pattern. For the determination of insulin sensitivity a 1-hour priming dose--constant infusion technique was used. Two 30-minute-periods of insulin infusion (8 and 16 mU/kg, primed by a start injection of 1 and 2 mU/kg, respectively) provoked a decrease of plasma glucose and FFA concentrations by 35 +/- 12.5% and 55 +/- 30.2%, respectively. Values lower than 22.5% (glycemia) or 25% (FFA) indicate a diminished insulin responsiveness. The metabolic clearance rate of insulin did not change at several concentrations of IRI. Thus, the proposed procedure is suitable to study the insulin sensitivity in vivo.
Thirty-eight non-obese and seven obese subjects were classified by a 2-hour glucose infusion test as having a normal carbohydrate tolerance. Sixteen non-obese ad ten obese patients showed a pathological carbohydrate tolerance (asymptomatic diabetes). For the characterization of insulin sensitivity a 1-hour priming dose-constant infusion technique consisting of two 30-minute-periods was applied in all subjects. A decrease of glycemia during this insulin infusion of less than 22.5 per cent has been accepted as a criterion of insulin insensitivity. Sixty-three per cent of non-obese and seventy-eight per cent of obese asymptomatic diabetics exhibited a reduced responsiveness to insulin. There ws an inverse relationship between the per cent decrease of plasma glucose concentration and the insulin secretion pattern revealed by the glucose infusion test. The results suggest that insulin resistance is a characteristic feature of obese and non-obese asymptomatic diabetics.
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In twenty-four non-obese male subjects a 2-hour glucose infusion test (12 mg/kg/min) with initial bolus injection (0.33 g/kg) was performed as a test of carbohydrate tolerance. Sixteen individuals had a normal and eight a pathological carbohydrate tolerance (asymptomatic diabetes). All subjects received a one-hour insulin infusion (two 30-minutes periods of 8 or 16 mU/kg MC-Actrapid). After two days subcutaneous adipose tissue was removed from the abdominal wall by needle biopsy for characterization of insulin-stimulated (1-14C) glucose incorporation into triglycerides. Under in vivo conditions insulin provoked a decrease of blood glucose concentrations by 31 +/- 3.9% and 11.6 +/- 2.2% as well as of plasma free fatty acids levels by 60 +/- 4.6% and 37 +/- 6.8% in normal persons and asymptomatic diabetics, respectively (p less than 0.01). In vitro the insulin-stimulated incorporation of labeled glucose into triglycerides of adipose tissue was diminished in asymptomatic diabetics. Thus, the results indicate that both the in vivo insulin responsiveness and the in vitro insulin sensitivity of adipose tissue are reduced in early stages of diabetes. The findings suggest that changes in insulin target tissues are equally important in the development of carbohydrate intolerance in non-obese subjects.
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Before the beginning of a glucose infusion test already in the test preperiod a stress-induced STH-increase could be observed in 76 of 153 protodiabetics. There was no statistically clear relation between the STH basal value and the size of the STH reaction. The stress-induced STH reaction neither can be classified to the degree of the carbohydrate intolerance nor to the size of overweight. In a normal STH reaction during the glucose infusion test in about two thirds of the cases a stress-induced STH increase is observed. On the other hand a rigid STH reaction is associated with a stress-induced STH increase only in 21% of the cases and a paradoxal STH reaction in 41% of the cases. Only in 47 (30.7%) of 153 protodiabetics a STH increase was to be observed before and after the end of the glucose infusion. There was no statistically certain relation between the size of the stress-induced increase of STH and the STH reaction in the posthyperglycemic phase. Quality and quantity of the STH reaction before the beginning of a glucose infusion do not allow any conclusions to the following pattern of STH reaction.
The pancreatic glucagon (IRG) secretion pattern was studied during a 2 h glucose infusion test (12 mg/kg/min) in 21 controls as well as in 44 subjects showing different degrees of carbohydrate intolerance. The fasting IRG levels increased significantly from controls (98 +/- 7.6 pg/ml) to chemical (144 +/- 9 pg/ml) and mild maturity-onset-type diabetics (166 +/- 12.2 pg/ml). During artificial hyperglycaemia the glucagon concentrations decreased slightly in all groups, but they remained at a higher level in early and overt diabetics). The molar IRI-IRG ratios have been found to be diminished in patients displaying a disturbed carbohydrate tolerance. There was not any correlation between insulin and glucagon concentrations in the blood. The findings suggest that abnormalities of alpha cell function may be present in early and overt diabetes independent of beta cell responsiveness. The causal relationship of A and B cell function in glucose intolerant subjects has to be cleared in follow-up studies.
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