Metasomatotrophic diabetes and its induction: Basal insulin secretion and insulin release responses to glucose,glucagon, arginine and meals

Summary Growth hormone treatment produced somatotrophic diabetes, with hyperglycaemia, polyuria, glycosuria and elevation in serum non-esterified fatty acids (NEFA) in dogs. Early in this diabetes, fasting serum immunoreactive insulin (IRI) rose 20-fold, the insulin/glucose (I/G) ratio rose 10-fold and in response to glucose infusion, the rise in IRI was twice the normal. In the latter half of the continued growth hormone treatment, the intensity of the diabetes increased, serum IRI declined to the normal level and the I/G ratio became subnormal. Late in the treatment, following glucose infusion, there was no change in serum IRI, no fall in NEFA and further depression of glucose tolerance. In metasomatotrophic diabetes, in which hyperglycaemia, glycosuria and high NEFA level persisted, fasting serum IRI was normal during several months, then became subnormal and the I/G ratio was diminished further. Following glucose IV there was no change in serum IRI, no fall in NEFA and low glucose tolerance. The normally-occurring rises in serum IRI following arginine and glucagon IV and after the ingestion of a meal were absent. These permanently diabetic dogs were responsive to insulin IV. The insulin content of the pancreas was reduced to about 1.2% of the normal after 14 months of this diabetes. From the sequence of change it is concluded that growth hormone induced metasomatotrophic diabetes by causing excessive secretion of insulin under basal and stimulative conditions, leading to permanent loss of function of the beta cells of the pancreatic islets, to such an extent that basal insulin secretion was low and the ability to secrete extra insulin in response to stimuli was lost.     

Growth hormone and metasomatotrophic diabetes: effects on insulin and proinsulin of serum and pancreas in dogs

Summary In normal fasting dog serum, the insulin: proinsulin molar proportion was 71:29%. In response to glucose infusion, the proinsulin proportion decreased. In the pancreas, the proinsulin proportion was lower than in serum. Growth hormone treatment for one day increased serum insulin sevenfold and proinsulin 18-fold. The proinsulin proportion increased to 49%. The growth hormone injections magnified the response to glucose infusion. The rise in serum insulin was 16 times the normal, proinsulin also rose but its proportion decreased. Growth hormone treatment for 6 days decreased pancreatic insulin to 5% and proinsulin to 46% of normal. In the permanent (metasomatotrophic) diabetes produced by the prolonged administration of growth hormone, serum insulin decreased and the proinsulin proportion increased. No rises in serum insulin nor proinsulin occurred following glucose infusion. In the pancreas, insulin and proinsulin were reduced to 1.6% and 8% of normal. The reduction in the immunoreactive insulin of the pancreas was more pronounced in the tail than in the head and body regions. The results indicate that in the state of augmented insulin secretion and hyperinsulinaemia produced by growth hormone and in the reduced insulin secretion and hypoinsulinaemia of metasomatotrophic diabetes, the proportion of proinsulin in serum is increased due to beta cell secretion containing a higher proportion of proinsulin than normal.     

Insulin,glucagon, and somatostatin release from the prediabetic Chinese hamster

Summary Diabetes mellitus in the adult Chinese hamster is characterized by subnormal pancreatic insulin release in vitro, decreased insulin content, and lack of obesity. The cause of the islet B-cell failure is not clear. We measured insulin, glucagon, and somatostatin release from in vitro perfused pancreases of young (mean age 10 and 20 weeks), genetically diabetic animals (subline AC, mean plasma glucose 8.0 and 16.6mmol/l, respectively). Compared to age- and sex-matched normal hamsters (subline M, mean plasma glucose 5.3 mmol/l), the younger diabetic animals had a significantly elevated mean plasma glucose level, but net in vitro pancreatic release of insulin, glucagon, and somatostatin was normal. Pancreatic content of insulin and glucagon was also not significantly different from normal. At age 20 weeks, when the plasma glucose of the diabetic animals was even more elevated, pancreatic content and release of insulin were significantly subnormal, whereas glucagon and somatostatin release were normal, and pancreatic content of glucagon was normal. In a similar group of young (mean age 10 weeks) diabetic animals, non-fasting plasma insulin levels were within the normal range, but the corresponding glucose levels were excessive in most of the animals (13 out of 19). In conclusion, 10-week-old diabetic hamsters show mild hyperglycaemia which cannot be accounted for directly by decreased pancreatic release in response to a glucose plus arginine stimulus in vitro. Decreased ability of the B cell to respond in vivo to hyperglycaemia or peripheral resistance to insulin may contribute to later B-cell failure in the older diabetic hamster.     

Divergent effect of glucagon antibodies on arginine and glucose-stimulated insulin secretion in the rat

Summary The effects of glucose and arginine on insulin secretion in the presence of glucagon antibodies were investigated in rats in vivo. In contrast to controls, animals given glucagon antibodies showed an inhibition of arginine-stimulated (p < 0.001), but not glucose-stimulated, insulin secretion. That these effects were not due to incomplete neutralisation of endogenous glucagon is evidenced by the presence of large antibody excess throughout the duration of the experiments. Both the glucagonotropic effect of arginine (319 ± 60ng/l, p < 0.01) and the insulinotropic effect of exogenous glucagon (8.3 ± 0.8 g/l, p < 0.001) were demonstrable under our experimental conditions in the absence of exogenous glucagon antibodies. These observations suggest that different mechanisms are involved in the stimulation of insulin release by arginine and by glucose, and that glucagon may play an important physiological role in the mediation and regulation of insulin secretion by secretogogues, such as arginine.     

Insulin and glucagon release in the diabetic Chinese hamster: Differences among inbred sublines

Summary Release of insulin and glucagon from perfused pancreases in vitro of 40 normal male and female Chinese hamsters (from one inbred subline) and 110 male and female diabetic hamsters (from three inbred sublines) was measured in response to glucose plus arginine, theophylline alone, or potassium alone, in order to determine if differences in hormone secretion exist among different diabetic sublines. Glucose plus arginine and potassium produced subnormal insulin responses in all three diabetic sublines, whereas theophylline induced normal or above normal insulin responses. Excessive glucagon release was consistently seen in only one diabetic subline. The female normal animals showed greater insulin release than the male normal hamsters in response to glucose plus arginine. This sex difference was not seen in the diabetic animals.     

Effect of furosemide on insulin and glucagon responses to arginine in normal subjects

Summary This study aimed at evaluating the influence of furosemide upon insulin and glucagon responses to arginine in healthy subjects. For this purpose, six normal subjects received two consecutive arginine pulses (3 g), 60 min apart, before and after the administration of furosemide (40 mg, IV). The acute insulin response (mean change from 3–10 min) to the second arginine pulse was significantly inhibited by furosemide (mean increase: 14.8 ±3.0 U/ml versus 11.7±2.5 U/ml, p<0.01). By contrast, the acute glucagon response was significantly increased (mean increase: 77±18 pg/ml versus 105±21 pg/ml, p<0.01). No significant changes in plasma glucose levels occurred. In control experiments, in which saline rather than furosemide was administered, the acute insulin and glucagon response to the first arginine pulse did not differ from that observed with the second pulse. The effect of furosemide on insulin and glucagon secretion might be mediated through enhanced release of endogenous prostaglandin E.     

Insulin and glucagon secretion in diabetic and non-diabetic patients with circulating islet cell antibodies

Summary Thirty-nine patients (14 non-diabetics, 8 chemical diabetics, and 17 overt diabetics) with circulating islet cell antibodies (ICA) were studied. Insulin and glucagon secretion after oral (100 g) and intravenous glucose loading (200 mg/kg bolus injection followed by an infusion of 20 mg/min over 60 min) and arginine infusion (25 g over 30 minutes) were evaluated in these patients and in non diabetic and diabetic ICA-negative controls. In the non-diabetic groups with or without ICA, insulin and glucagon responses to glucose were similar. Moreover, in ICA positive patients the response of these hormones to arginine infusion was reduced. Similar alterations in insulin and glucagon secretion were observed in the ICA positive and negative patients with chemical or overt diabetes. In particular, fasting hyperglucagonaemia and glucagon hyperresponse to arginine are associated with a lack of insulin secretion in the patients with overt diabetes. Hormonal differences between diabetics with and without ICA could not be detected.This work was previously presented at the 12th Meeting of the European Association for the Study of Diabetes, Helsinki, September 1976 and published in abstract form in Diabetologia12, 422 (1976)     

Does glucagon play a role in the insulin resistance of patients with adult non-ketotic diabetes?

Summary Using a constant intravenous infusion technique we have measured in vivo insulin resistance in 17 normal subjects, five patients with chemical diabetes, and 13 non-ketotic diabetic patients with fasting hyperglycaemia (FBS>120 mg/ 100 ml). All of the diabetic patients were non-obese. The results demonstrated that the diabetic patients were insulin resistant compared to normals and that the degree of insulin resistance was greater the more severe the diabetes. No differences in plasma glucagon levels were found among the different groups during the infusion studies. These results demonstrate that non-obese, non-ketotic diabetic patients are insulin resistant and that abnormalities in plasma glucagon concentrations do not account for this insulin resistance.Dr. Olefsky is a Clinical Investigator with the Veterans AdministrationDr. Sperling is a recipient of a Research Career Development Award from the U. S. P. H. S., 1K04-HD 00029Dr. Reaven is a Medical Investigator with the Veterans Administration     

The mechanism of exaggerated glucagon response to arginine in diabetes mellitus

As far as exaggerated arginine-induced glucagon secretion in diabetics is concerned, the authors have shown that both the restoration of blood glucose excursions and physiological insulinemia in response to arginine, obtained from an artificial endocrine pancreas (AEP) could normalize the glucagon secretory responses in diabetes mellitus. To clarify whether or not physiological glycemic excursions and/or plasma insulin profiles contribute to the normalization of the exaggerated glucagon response in diabetes mellitus, the following 4 investigations were conducted on each of 7 non-obese, non-insulin-dependent diabetic (NIDDM), and 8 insulin-dependent diabetic (IDDM) subjects, with the aid of AEP. Arginine was i.v. infused into both diabetic groups (1) in a hyperglycemic state without insulin infusion, (2) in perfect glycemic control with insulin infusion by AEP, (3) in glycemic control with AEP, but with lower plasma insulin profiles (parameters of the insulin infusion algorithm were made smaller than those of (2], (4) in a state where blood glucose levels were clamped at the same levels as obtained in (1) with the aid of glucose infusion controlled by AEP, and where physiological plasma insulin profiles were mimicked by infusing insulin at the same rates used in (2) with a pre-programmable insulin infusion system. The changes in the plasma glucagon (IRG) response in each experiment were compared with those seen in healthy subjects. For both diabetic groups it was found that: in (2) perfect normalization of glucagon response was achieved.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute insulin response to intravenous glucose,glucagon and arginine in some subjects at risk for Type 1 (insulin-dependent) diabetes mellitus

Summary The relationships between first-phase insulin secretion to i.v. glucagon and i.v. arginine were studied in 19 healthy adult volunteers (Group I) and in 21 subjects at risk for Type 1 (insulin-dependent) diabetes mellitus with either a normal (n=11; Group II a) or a low insulin response to i.v. glucose (n=10; Group II b). Groups I and II a displayed similar insulin responses to the three secretagogues. In contrast, Group II b demonstrated lower insulin responses to both glucagon and arginine than control subjects (p}<0.007 and (p}<0.04 respectively) orthan normo-responders to glucose (#x007D;<0.007 and p<0.04 respectively). In Group II b however, arginine-stimulated insulin release was increased compared to the response to glucose (p}<0.006), while glucagon and glucose led to non-statistically different responses. Five low-responders developed Type 1 diabetes. As a group, they displayed lower responses to glucagon and to arginine than subjects who up to now have not developed the disease (p<0.05 and p<0.0003 respectively). In the subjects who progressed to diabetes, the responses to glucose and glucagon were similarly blunted. In the low-responders who have not developed the disease, no statistical difference could be detected between mean responses to glucagon and glucose, but four out of these five subjects had a glucagon-stimulated response within the control range and higher than their corresponding response to glucose. Arginine led to a higher stimulation than glucose, in subgroups that either progressed to diabetes (p<0.006) or did not (p<0.002). Finally, low-responders who did not develop diabetes displayed similar responses to both glucagon and arginine than normo-responders to glucose. A progressive decrease of arginine-stimulated insulin response may be a later event during pre-Type 1 diabetes than a blunted response to glucose, while a loss of glucagon-stimulated insulin release may be intermediate. Diminished response to all secretagogues may offer better prediction than a low response to glucose alone.     

Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine

Summary Quantitative determination of insulin secretion is of importance both clinically and in research. The optimal method has not been established, although several different methods have been used. We determined the reproducibility of islet function parameters obtained by the glucose-dependent arginine stimulation test, and also studied the priming effect of arginine on subsequent acute insulin responses. The test measures the acute insulin (AIR) and glucagon (AGR) responses to i. v. arginine (5 g injected over 45 s) at fasting glucose and glucose concentrations clamped at 14 and above 25 mmol/l, as well as the glucose potentiation of insulin secretion (slope_AIR) and the glucose inhibition of glucagon secretion (slope_AGR). When the test was performed twice in seven healthy women (mean ± SD age 58.7 ± 0.5 years, BMI 27.6 ± 5.5 kg/m²), the AIRs to arginine had a within-subject coefficient of variation (CV) of 18.6 % at fasting glucose, 18.7 % at 14 mmol/l glucose and 16.3 % at above 25 mmol/l glucose. The CVs for AGR were 11.6, 14.9 and 8.9 %, respectively. The CV of the slope_AIR was 24 % and of the slope_AGR 17.2 %. The arginine priming study was performed in six healthy women (age 63.7 ± 0.3 years, BMI 28.0 ± 6.9 kg/m²). Saline or arginine (5 g) was injected at fasting glucose, followed by arginine (5 g) at 14 mmol/l glucose. There was no difference between the acute insulin or glucagon responses to arginine at 14 mmol/l glucose in the two conditions, suggesting that there is no priming effect of arginine on the subsequent acute insulin or glucagon responses. Therefore, this method is a good tool to determine insulin secretion as, apart from its good reproducibility, it also provides several important parameters of islet function. [Diabetologia (1998) 41: 772–777] Received: 4 December 1997 and in final revised form: 13 February 1998     

Insulin delivery rate in response to glucose and arginine infusion in hyperthyroidism

Summary Insulin delivery rates were estimated from the peripheral serum insulin response to a single bolus injection of glucose or arginine in eight normal subjects and eight patients with hyperthyroidism. The mean rate constant for insulin disappearance was 0.2380±0.0052 per min in the control subjects, which was not significantly different from that observed in the patients with hyperthyroidism (0.2147±0.0111 per min). There were also no significant differences in the insulin response to glucose infusion (1.7±0.3 U during the first phase (0–10 min) and 5.6±1.6 U during the second phase (11–60 min) in normal subjects compared with 1.2±0.5 and 3.7±1.1 U respectively in the hyperthyroid patients). The delivered insulin in response to glucose infusion was similar in the two groups. The kg-value in the patients with hyperthyroidism was lower than that in the control subjects (1.24±0.11 versus 2.11±0.22;p < 0.005). In hyperthyroidism, the low kg-value was not a result of the diminished insulin delivery to the general circulation. Insulin delivery showed a monophasic pattern following arginine infusion in both patients and control subjects. For the control subjects, the amount of insulin delivered was estimated to be 0.53±0.12 U during the first 10 min and 0.37±0.14 U during 11–30 min. In hyperthyroidism, the amount of insulin delivered was significantly lower than in the control subjects (0.21±0.06 U during the first 10 min and 0.07±0.03 U during 11–30 min). In the control subjects, the plasma glucose level was raised transiently following arginine infusion, but in hyperthyroidism, there was no change in plasma glucose levels. In hyperthyroidism, therefore, glucose intolerance appears to be primarily related to an antagonism of the hepatic effect of insulin by thyroxine rather than an inhibitory effect of thyroxine on insulin secretion. However, since delivery rate represents the measurement of peripheral serum insulin concentrations, these results cannot exclude an abnormality of hepatic insulin metabolism in hyperthyroidism.     

Effect of a long acting glucagon selective somatostatin analogue on plasma glucose,insulin and glucagon levels in the anaesthetized rat during arginine infusion

Summary The effects of somatostatin and a long acting, glucagon selective somatostatin analog (des-Ala¹Gly²[His^4,5-D-Trp⁸]-somatostatin), were studied during arginine tolerance tests in normal anaesthetized rats. Arginine infusion in control animals resulted in a rapid increase in plasma insulin and glucagon, and an increase of 15±5 mg/dl in plasma glucose. Somatostatin infusion (1 mg/kg/h) resulted in suppression of basal insulin secretion and a decrease in arginine-induced insulin and glucagon release. Glucose levels increased rapidly during the combined arginine-somatostatin infusion reaching a peak of 72±10 mg/dl above basal levels. Similar results were obtained when somatostatin was injected SC (1 mg/kg) at times 0, 15, 30, and 45 minutes (arginine infused from 30–60 minutes). A single injection (1 mg/kg) of the long-acting somatostatin analogue resulted in significant inhibition of basal insulin and glucagon release; during arginine infusion glucagon levels rose only slightly, the insulin response was, however, nearly normal, and only a small arginine-induced increase in glucose levels was observed. Carbohydrate absorption was not influenced by either somatostatin or the analogue.     

Failure of indomethacin to affect arginine-induced C-peptide and glucagon release in insulin-treated diabetics

Summary Fourteen insulin-treated diabetics were submitted to an arginine infusion test performed with either 11.7 or 5.85mg kg^-1 min^-1 arginine monohydrochloride infused during 40 min with or without previous oral administration of a low (75+50 mg) or a high (75 mg + 3 mg/kg) dose of indomethacin. Blood glucose, plasma non-esterified fatty acids, insulin, C-peptide and glucagon were determined at regular intervals before, during and after the arginine infusion. These parameters were totally unaffected by the two doses of indomethacin both in the basal state and during the arginine infusions at the two loads tested. Eight subjects had a basal C-peptide level above 0.07 pmol/ml and a mean (± SEM) maximal rise of 0.21±0.04 pmol/ml during the arginine infusion, whereas the remaining six patients had virtually zero values throughout the tests. The arginine-induced plasma glucagon rise was similar for the two rates of arginine infusion; the sum of the increments in plasma glucagon averaged 877±120 and 647±92 pg/ml (p>0.1) for the high and low rates of arginine infusion, respectively. The magnitude of the blood glucose rise appeared independent of the amount of arginine infused. Confirming previous reports, we found that the blood glucose rise after arginine was three to four times higher in subjects without C-peptide than in subjects with C-peptide. The mean glucagon response did not differ significantly between subjects with or without C-peptide. Thus, residual B cell function determines the magnitude of the blood glucose rise but not the glucagon response after intravenous arginine.     

Absence of glucopenic inhibition of the insulin response to arginine at the onset of diabetes in BB/W rats

Summary To determine if the inhibiting effect of glucopenia on arginine-stimulated insulin secretion is impaired at the onset of autoimmune diabetes, the insulin response to arginine was studied at 5.6 and 2.8 mmol/l glucose in perfused pancreata isolated from BB/W rats on the first day of diabetes and from age-matched diabetes-prone BB/W rats without diabetes. During glucopenia the baseline insulin secretion was reduced by more than 80% in both groups. However, the arginine-stimulated insulin response in the diabetic group was only 16.5% lower during glucopenia compared to 79.1% lower in the nondiabetic controls. Also, enhancement of the arginine-stimulated glucagon response by glucopenia was modest compared to controls. The results indicated that at the onset of this form of autoimmune diabetes the surviving B cells are, for unknown reasons, hyperresponsive to arginine and that, in contrast to the controls, this response is not inhibited by glucopenia.     

Lack of influence of arginine preloading on the insulin response to I.V. glucagon in children and adolescents

Summary Nine normal children (6 males and 3 females) aged from 7 1/2 to 14 1/2 years underwent a 30-min arginine infusion (0.5 g/kg) followed at 90 min by one bolus i.v. glucagon injection (0.03 mg/kg). On a separate occasion the same children underwent an i.v. glucagononly test. No significant difference was found when the glucose and insulin responses in the two glucagon tests were compared, in contrast to previous findings that preloading with glucose resulted in a significantly increased response of insulin to glucagon. Established Investigator of the Chief Scientist’s Bureau Ministry of Health.     

Clinical evaluation of somatostatin as a potential adjunct to insulin in the management of diabetes mellitus

Summary To determine whether somatostatin, an inhibitor of glucagon and growth hormone secretion, might be useful as an adjunct to insulin in the management of diabetic hyperglycaemia, seven insulinrequiring diabetic men were given somatostatin (100 g/h, IV) continuously for 3 days after their diabetes had been treated intensively by diet and insulin on a metabolic ward. During infusion of somatostatin and despite reduction in average insulin dose exceeding 50%, there was improvement in diabetic control as assessed by postprandial hyperglycaemia, 24-h glycosuria and the average daily serum glucose level and its fluctuation; when somatostatin was discontinued, but insulin doses held constant, diabetic control rapidly worsened. No adverse effects were observed. These results indicate that somatostatin plus insulin can be a more effective regimen than insulin alone in controlling diabetic hyperglycaemia. A longer acting and more selective somatostatin preparation may prove useful as an adjunct to insulin in the management of diabetes.     

Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man

Summary We have studied the effects of vitamin D deficiency on pancreatic A- and B-cell function. Four subjects with vitamin D deficiency and 10 healthy subjects were studied. Pancreatic B-cell function was assessed by the insulin response to an oral glucose tolerance test. An insulin tolerance test was used to evaluate pancreatic A-cell function. The patients were then treated with 2000 U/day of vitamin D₃ for 6 months, after which the clinical, metabolic, biochemical and radiological features of vitamin D deficiency resolved, and pancreatic A-and B-cell function was repeated. In the vitamin D-deficient subjects pre-treatment and post-treatment serum calcium levels (mean±SEM) were 2.22±0.01 mmol/l and 2.24±0.01 mmol/1 respectively, and 2.27 ± 0.02 mmol/l in healthy subjects (NS). The pre-treatment level of 1,25-dihydroxy vitamin D (1,25-(OH)₂D) of 29.7 ± 3.3 pg/ml in the vitamin D deficient subjects rose to 70.3±10.3pg/ml after treatment (p < 0.05). The 1,25-(OH)₂D level in the healthy subjects was 50.0 ± 13.7 pg/ml (p < 0.05 versus pre- and post-treatment values in the patients). Insulin secretion, calculated by the area under the insulin curve, was significantly lower before vitamin D₃ treatment in the patients (9.09±0.7 mU × min,p<0.05) compared with the healthy subjects (11.9±0.5 mU × min) and post-treatment values of the patients with vitamin D deficiency (13.7 ± 0.5 mU x min). Similar changes were seen in the insulogenic indicesΔ I/ΔG). WhileΔI/ΔG was 1.71±0.4 (mean ± SEM) during vitamin D deficiency, it increased to 2.48±0.3 with vitamin D repletion. The insulogenic index in the healthy subjects was 2.68±0.3. The glucose areas were not significantly different. Insulin-induced glucagon secretion was similar in all instances. The results of this study suggest that vitamin D deficiency reduces pancreatic insulin secretion but it does not affect pancreatic A-cell function.     

Diurnal patterns of blood glucose,serum free fatty acids,insulin, glucagon and growth hormone in normals and juvenile diabetics

Summary Blood glucose, serum free fatty acids,-insulin, -glucagon and -growth hormone have been measured half-hourly in five newly diagnosed, untreated, male patients with classic juvenile diabetes and in five healthy male subjects during a 24-h period of daily life. —Blood glucose, serum insulin and -free fatty acids followed, on the whole, the expected pattern. Serum gluoagon showed a fairly constant level during day and night in both groups. — In the non-diabetic subjects, serum growth hormone was low during most of the day. Only two peaks were observed before 10 p.m. Four of the subjects showed peaks at precisely the same time, namely at 10.30 p.m. and 1.30 a.m. Two showed peaks at 5.00–5.30 p.m. The mean serum growth hormone concentration during the 24-h period was 1.98 ng/ml. — In the juvenile diabetics, the growth hormone was higher and the level fluctuated much more, showing more frequent and higher peaks than in the non-diabetics. The mean serum growth hormone concentration during the 24-h period was 7.26 ng/ml, i.e. three to four times higher than in the non-diabetics.

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Tagesrhythmen des Blutzuckers und der Serumspiegel der freien Fettsäuren, des Insulins, des Glucagons und des Wachstumshormons bei Normalpersonen und jugendlichen Diabetikern

Zusammenfassung Bei gesunden Männern und 5 männlichen Patienten mit dem klassischen Bild eines frisch entdeckten, unbehandelten, jugendlichen Diabetes wurden in halbstündigen Abständen der Blutzucker und die Spiegel der freien Fettsäuren, des Insulins, des Glucagons und des Wachstumshormons im Serum während einer 24 Std-Periode des Tagesablaufs bestimmt. —Die Tageskurven für Blutzucker, freie Fettsäuren und Seruminsulin zeigten dabei im ganzen den erwarteten Verlauf. Das Serumglucagon wies in beiden Gruppen bei Tag und Nacht recht konstante Werte auf. — Bei den Normalpersonen fanden sich den größten Teil des Tages niedrige Wachstumshormon-Spiegel. Nur 2 Gipfel wurden vor 22 Uhr beobachtet. 4% der Kontrollpersonen zeigten solche Maxima genau gleichzeitig, nämlich um 22.30 und um 1.30 Uhr. Bei 2 ließen sich Gipfel um 17 Uhr und 17.30 nachweisen. Die durchschnittliche Wachstumshormon-Konzentration während der 24 Std-Periode betrug 1.9. — Bei den jugendlichen Diabetikern lagen die Werte für das Wachstumshormon höher, schwankten stärker und zeigten mehr und höhere Gipfel als bei den nichtdiabetischen Vergleichspersonen. Der mittlere Wachstumshormon-Spiegel betrug während der 24 Std-Periode 7.26 ng/ml, lag also 3–4 × höher als beim Kontrollkollektiv.

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Schéma d'évolution de la glycémie, des acides gras libres, de l'insuline, du glucagon et de l'hormone de croissance dans le, sérum, chez des sujets normaux et des diabétiques juvéniles

Résumé La glycémie, les acides gras libres, l'insuline, le glucagon et l'hormone de croissance sériques ont été mesurés toutes les demi-heures chez cinq patients de sexe masculin, atteints de diabète juvénile classique, récemment diagnostiqué et non traité, et chez cinq sujets de sexe masculin en bonne santé pendant une période de 24 h. — La glycémie, l'insuline et les acides gras libres du sérum suivaient dans l'ensemble le schéma attendu. Le taux de glucagon sérique était assez constant pendant le jour et la nuit dans les deux groupes. -Chez les sujets nondiabétiques, l'hormone de croissance du sérum était basse pendant la plus grande partie du jour. Deux pics seulement ont été observés avant 10 h du soir. Quatre des sujets ont eu des valeurs élevées exactement au même moment, c'est-à-dire à 10.30 h du soir et à 1.30 h du matin. Deux ont eu des valeurs élevées à 5 h – 5.30 h de l'après-midi. La concentration moyenne d'hormone de croissance du sérum pendant la période de 24 h était de 1.98 ng/ml. — Chez les diabétiques juvéniles, l'hormone de croissance était plus élevée et le taux variait beaucoup plus, monttrant des pics plus fréquents et plus élevés que chez les non-diabétiques. La concentration moyenne d'hormone de croissance du sérum pendant la période de 24 h était de 7.26 ng/ml, c'est-à-dire une concentration trois sà quatre fois plus élevée que chez les non-diabétiques.