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Biomedical subjects

A Diana

Publications and source records attributed to A Diana.

43 records · Page 3Linked to original sources

Insulin resistance in the aged: the role of the peripheral insulin receptors.

In the healthy subject, glucose tolerance tends to decrease with age due to impaired insulin secretion and/or decreased peripheral insulin activity. An oral glucose (100 g) tolerance test was performed on 12 aged (70 +/- 4 yr) and 8 young (32 +/- 7 yr) subjects; these subjects underwent laparatomy for cholecystectomy or the management of abdominal diseases. Subcutaneous adipose tissue was removed during surgery and fat cells, prepared according to a personal modification of Rodbell's method, were incubated in a medium containing monoiodo- and cold insulin to evaluate insulin binding and affinity constants. The results of the tolerance test pointed to an insulin resistant state i.e., impaired glucose tolerance coupled with normal plasma insulin, as previously shown also by us using other methods in the aged subject. The binding study demonstrates a distinct insulin receptor decrease in fat cells from the older subjects (185,000 +/- 19,200 as opposed to 310,000 +/- 12,000), without any change in affinity constants. The result indicates that insulin resistance in the aged may be attributed at least in part to a reduction in the number of insulin receptors on the target cells. This could be a consequence of aging itself, as proposed by other workers in the case of old fat rats.

Adipose Tissue↗

Effects of a xanthine derivative (BL 191) on insulin secretion in normal man.

A xanthine derivative, named BL-191, was administered iv in 8 healthy volunteers alone and in association with glucose (0.33 g/kg body weight iv) or glybenclamide (1 mg iv). BL-191 was infused iv at a constant rate in a dose of 200 mg during 45 minutes. Blood glucose, free fatty acids and immunoreactive insulin were measured during one hour. It was impossible to demonstrate neither a direct effect nor an enhancement of insulin secretion during drug administration; in another experiment (treatment F) a higher dosage of BL-191 (100 mg as a priming dose + 200 mg as infusion dose) was likely ineffective. It appears that some difference in insulin response may be present in the single subject (not evident in the mean), indicating a difference in the beta-cell cAMP-system sensitivity in individuals. These negative results allow some considerations on the importance of the beta-cell cAMP-system in healthy human beings.

Adult↗

Diurnal variations in insulin secretion and insulin sensitivity in aged subjects.

Glucose tolerance tends to decrease in healthy aged subjects without family history of diabetes. Either reduced insulin secretion or insulin resistance may be responsible. Insulin secretion and insulin sensitivity were studied in 7 aged subjects (68-75 years) and 8 young controls (21-27 years). A 1-mg i.v. glucagon and a 5-U/m2 body area i.v. insulin test were run in each subject at 07(00) and at 19(00) on two different days to detect diurnal variations. An arginine test was also performed to evaluate pancreatic glucagon behavior. In the evening, young subjects presented a glucose tolerance impairment with significantly decreased plasma insulin levels, and a reduced hypoglycemic effect of exogenous insulin. Resistance to both endogenous and exogenous insulin in the aged was observed in the morning without significant morning/evening variations. Since the response to contra-insular hormones (GH in the insulin test, glucagon in the arginine test) was the same in both age groups, their role in the phenomenon could be ruled out. It is suggested that in the aged a stable reduction in number and/or a change in affinity of insulin receptors may occur. In addition, since aging is seen to be associated with the disappearance of diurnal variations in glucose tolerance and insulin secretion and sensitivity, and since a reduction in the receptor level of young healthy subjects in the evening has been reported by some authors, it is suggested that aged subjects may be less able to modulate the binding of insulin to its peripheral receptors in the course of the day.

Adult↗

IL-1beta and ICE mRNA are not altered upon beta-amyloid(25-35) induced neurotoxicity in human neuroblastoma cells.

The specific beta-amyloid(25-35) fragment induced cellular degradation of the human neuroblastoma cell line SH-SY5Y, but did not elicit an effect on the levels of interleukin-1beta and interleukin-1beta converting enzyme, as determined by semiquantitative reverse transcription-polymerase chain reaction and immunocytochemical analysis. The assays revealed constitutive expression of these proteins both at mRNA and protein level. It is conceivable that in the absence of glial elements, such as in the present neuroblastoma cell line, beta-amyloid triggers the toxicity through a direct action and/or through the production of other harmful molecules.

Amino Acid Chloromethyl Ketones↗

[Immunological changes in diabetes mellitus. Study of lymphocyte populations].

In view of some data of the literature suggesting that immunological changes could play a role in the pathogensis of diabetes mellitus and of its complications, we carried out a study of the lymphocyte populations of 44 diabetic subjects by means of E, EA, EAC rosettes and membrane immunofluorescence. A quarter of the patients had decreased E rosettes: all of these had long-lasting, insulin-dependent, poorly controlled diabetes. Some of these patients had also increased membrane IgG globulins. In 5 patients with recent onset, insulin-independent diabetes, E rosettes were increased. No significant changes of EA and EAC rosettes were observed. These findings suggest that changes of lymphocyte populations do not play any role in the pathogenesis of diabetes, while these may be the consequence of the metabolic disorder and these may favour the onset of complications of the disease.

Adult↗