E4orf1-induced reduction in endogenous insulin level is independent of pancreas endocrine function

Author(s):  
Md Akheruzzaman ◽  
Vijay Hegde ◽  
Md Abu Bakkar Siddik ◽  
Zahra Feizy ◽  
Andrew C. Shin ◽  
...  
1981 ◽  
Vol 97 (3) ◽  
pp. 391-397 ◽  
Author(s):  
Karl-Göran Tranberg ◽  
Per Hagander ◽  
Jan Thorell

Abstract. Clearance rates of unlabelled insulin were studied in 45 unanaesthetized non-diabetic humans. The clearance rate, as well as the pancreatic secretion rate, of endogenous insulin was estimated from steady-state concentrations in portal and arterial blood. The clearance rate of exogenous insulin was determined after brief intraportal infusion. In the basal fasting state, the endogenous plasma insulin level varied as closely with the clearance of endogenous insulin as with the rate of pancreatic secretion. During elevation of insulin by glucose infusion, it varied predominantly with the rate of insulin secretion. Clearance of exogenous insulin did not vary with the pre-test endogenous insulin level. The clearance of endogenous insulin increased from 11 ml · min−1 · kg−1 in the basal fasting state to 17 ml · min−1 · kg−1 during glucose infusion. Clearance of exogenous insulin fell progressively with increasing dose, from 35 (8 mU/kg) to 14 (43 mU/kg) ml · min−1 · kg−1 at normoglycaemia and from 23 (8 mU/kg) to 17 (34 mU/kg) ml · min−1 · kg−1 at hyperglycaemia. The clearance of endogenous insulin was lower than that of exogenous insulin at normoglycaemia, but of similar size during glucose infusion. It is concluded that variation in clearance rate is partly responsible for variation in plasma insulin concentration, particularly in the basal fasting state, and that the clearance rate is lower in the basal state than otherwise. To some extent, the low clearance values for endogenous insulin in the basal state may reflect poor specificity of the insulin radioimmunoassay.


2019 ◽  
Vol 2019 ◽  
pp. 1-4 ◽  
Author(s):  
Einas Alrashidi ◽  
Thamer Alessa

Insulin autoimmune syndrome (IAS) is a disease characterized by hyperinsulinaemic hypoglycaemia associated with autoantibodies against endogenous insulin. We have described a case of a 25-year-old, previously healthy Kuwaiti man who was admitted to the Mubarak Al-Kabeer hospital with a history of recurrent hypoglycaemia. The patient revealed that he had taken several different injectable anabolic steroids and growth hormone with oral amino acids and other tablets (fat burners) for bodybuilding in the last two months. He denied knowingly using insulin or insulin analogues. The patient had elevated fasting insulin level (>301 uIU/mL) and elevated insulin autoantibodies (>100.0 IU/mL). After appropriate work-up, he was diagnosed with IAS. After treatment with prednisolone (1 mg/kg/day), the patient had complete recovery. In patients with repeated hypoglycaemia, IAS should be considered in the differential diagnosis. Glucocorticoid therapy can be effective for the treatment of hypoglycaemia in patients with IAS.


1983 ◽  
Vol 244 (3) ◽  
pp. E203-E208
Author(s):  
F. M. Hansen ◽  
P. Nilsson ◽  
B. E. Hustvedt ◽  
P. Nilsson-Ehle ◽  
A. Lovo

The significance of the hyperinsulinemia on the altered metabolism in ventromedial hypothalamus (VMH)-lesioned rats was tested. VMH lesions induced increases in fatty acid synthesis, lipoprotein lipase (LPL) activity, and plasma urea levels, and a decrease in plasma triglyceride concentrations. Similarly, in normal rats treated with pharmacological doses of insulin (14 U X rat-1 X day-1), fatty acid synthesis and LPL activity in fat tissue and the plasma urea were considerably elevated and plasma triglyceride was lowered compared with untreated controls. When endogenous insulin production was abolished by streptozotocin treatment, the four metabolic variables in the VMH-lesioned rats did not differ from those in diabetic controls. Substitution with 2 U of insulin X rat-1 X day-1, however, restored the differences in metabolism between VMH-lesioned diabetic and control diabetic rats. Substitution with 3 or 4 U insulin X rat-1 X day-1 showed the same differences. In VMH-lesioned rats the insulin level increased significantly from the 10th to the 70th day postoperatively; however, the rate of fatty acid synthesis, LPL activity, and plasma urea levels decreased, whereas plasma triglyceride concentrations increased. The results strongly suggest that the metabolic changes occurring after VMH lesions are only in part explained by the hyperinsulinemia associated with the VMH syndrome and indicate that other hormonal and/or nervous factors are involved.


Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.


1966 ◽  
Vol 53 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Torsten Deckert ◽  
Kai R. Jorgensen

ABSTRACT The purpose of this study was to investigate whether a difference could be demonstrated between crystalline insulin extracted from normal human pancreas, and crystalline insulin extracted from bovine and porcine pancreas. Using Hales & Randle's (1963) immunoassay no immunological differences could be demonstrated between human and pig insulin. On the other hand, a significant difference was found, between pig and ox insulin. An attempt was also made to determine whether an immunological difference could be demonstrated between crystalline pig insulin and crystalline human insulin from non diabetic subjects on the one hand and endogenous, circulating insulin from normal subjects, obese subjects and diabetic subjects on the other. No such difference was found. From these experiments it is concluded that endogenous insulin in normal, obese and diabetic human sera is immunologically identical with human, crystalline insulin from non diabetic subjects and crystalline pig insulin.


1970 ◽  
Vol 64 (2) ◽  
pp. 347-358
Author(s):  
A. Stanley Weltman ◽  
Arthur M. Sackler

ABSTRACT Body weight, metabolic rate, locomotor activity and alterations in endocrine organ activity were noted in recessive homozygous male whirler mice and the phenotypically »normal« heterozygotes. Representative populations of the two types were studied at different age levels. In general, body weights of the whirler mice were consistently and significantly lower. Open-field locomotion studies similarly indicated heightened locomotor activity. Total leukocyte and eosinophil counts were either markedly or significantly lower in the homozygous vs. heterozygous whirler groups. Evaluation of relative organ weights showed significantly increased adrenal weights in whirler mice sacrificed at 14 weeks and 11 months of age. These changes were accompanied by involution of the thymus. Thus, the varied data indicate persistent increased metabolism and adrenocortical activity during the life-span of the whirler mice. Seminal vesicle weight decreases in the whirler males at 11 months suggest lower gonadal function. The findings are in accord with previous studies of alterations in metabolic rates and endocrine function of homozygous whirler vs. heterozygous female mice.


1960 ◽  
Vol XXXIII (III) ◽  
pp. 388-400 ◽  
Author(s):  
L. G. Huis in 't Veld ◽  
B. Louwerens ◽  
P. A. F. van der Spek

ABSTRACT In two male patients and two castrated males, the influence of corticotrophin (ACTH) on the urinary excretion of neutral 17-ketosteroids and 17-hydroxycorticosteroids was determined before and during a period in which patients were treated with 5 mg 17α-methyl-19-nortestosterone (MNT) daily. In two castrated males, moreover, the influence of chorionic gonadotrophin and ACTH + chorionic gonadotrophin on the urinary excretion of 17-ketosteroids and 17-hydroxycorticosteroids was determined before and during a period of treatment with 5 mg MNT daily. Prolonged administration of MNT causes a decrease in the urinary excretion of neutral 17-ketosteroids and 17-hydroxycorticosteroids both in the normal males and in the male castrates. ACTH caused an increase in the urinary excretion of 17-ketosteroids and 17-hydroxycorticosteroids before and during MNT administration. During MNT administration this increase (expressed in mg/24 hours) was ≤ the increase produced by the same dose of ACTH prior to MNT administration. In two male castrates treated with MNT, chorionic gonadotrophin caused no increase in the urinary excretion of 17-ketosteroids and 17-hydroxycorticosteroids. The effect obtained before and during MNT administration by administration of ACTH + chorionic gonadotrophin did not exceed the effect obtained by the same dose of ACTH alone. Our conclusion is that the effect of MNT on the excretion of adrenocortical steroids is not due to the inhibition of the ACTH secretion. The possibility of a direct effect of MNT on the adrenal cortex has not been excluded with complete certainty. A change in the corticosteroid metabolism due to the influence of MNT, however, must also be taken into consideration.


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