Effects of Sublethal Whole-Body X-Irradiation on Glucose Tolerance in the Rat and the Guinea Pig

1960 ◽  
Vol 13 (1) ◽  
pp. 25
Author(s):  
Neda Šestan ◽  
Nikša Allegretti ◽  
Miloje Matošić ◽  
Magda Devčić ◽  
Neda Sestan ◽  
...  
1956 ◽  
Vol 188 (1) ◽  
pp. 76-80 ◽  
Author(s):  
Arthur B. French ◽  
Patricia E. Wall

Cholinesterase activity and responses to pressure, acetylcholine, histamine and eserine were studied in isolated intestinal loops from 15 rhesus monkeys, 4 rats and 31 guinea pigs subjected to whole body x-irradiation, and in loops from paired control animals. Ileal and jejunal nonspecific cholinesterase levels were reduced in rats 48 hours after 650 r, and in guinea pigs 48 hours after 250 r, but not in rhesus monkeys 48 hours and 7–9 days after 800 r. Monkey plasma cholinesterase levels showed only a small preterminal decrease when measured daily after 800 r. The peristaltic responses of monkey and guinea pig intestinal loops to intraluminal pressure were normal at the above intervals after radiation. In monkeys, rats and guinea pigs the dose of acetylcholine required to elicit a contraction was unchanged by radiation regardless of whether threshold dose or the dose which produced 50% of the calculated maximal response was measured. The height of the maximum contractile response of monkey ileal and jejunal loops to acetylcholine was greater at both time intervals after radiation than in control loops. This difference was not found in rats or guinea pigs or in monkeys after histamine or eserine. These observations cast doubt on the idea that changes in intestinal cholinesterase activity or in the sensitivity of intestinal muscle to acetylcholine play a significant part in the vomiting and the changes in intestinal motor activity which follow x-irradiation.


Science ◽  
1950 ◽  
Vol 111 (2874) ◽  
pp. 88-90 ◽  
Author(s):  
T. J. Haley ◽  
D. H. Harris
Keyword(s):  

Science ◽  
1950 ◽  
Vol 111 (2874) ◽  
pp. 88-90
Author(s):  
Thomas J. Haley ◽  
D. Harriette Harris
Keyword(s):  

1960 ◽  
Vol 13 (1) ◽  
pp. 31
Author(s):  
Nikša Allegretti ◽  
Miloje Matošić ◽  
Neda Šestan ◽  
Suzana Šlamberger ◽  
Niksa Allegretti ◽  
...  

Diabetologia ◽  
2021 ◽  
Author(s):  
Juliana de Almeida-Faria ◽  
Daniella E. Duque-Guimarães ◽  
Thomas P. Ong ◽  
Lucas C. Pantaleão ◽  
Asha A. Carpenter ◽  
...  

Abstract Aims/hypothesis Levels of the microRNA (miRNA) miR-126-3p are programmed cell-autonomously in visceral adipose tissue of adult offspring born to obese female C57BL/6J mice. The spectrum of miR-126-3p targets and thus the consequences of its dysregulation for adipocyte metabolism are unknown. Therefore, the aim of the current study was to identify novel targets of miR-126-3p in vitro and then establish the outcomes of their dysregulation on adipocyte metabolism in vivo using a well-established maternal obesity mouse model. Methods miR-126-3p overexpression in 3T3-L1 pre-adipocytes followed by pulsed stable isotope labelling by amino acids in culture (pSILAC) was performed to identify novel targets of the miRNA. Well-established bioinformatics algorithms and luciferase assays were then employed to confirm those that were direct targets of miR-126-3p. Selected knockdown experiments were performed in vitro to define the consequences of target dysregulation. Quantitative real-time PCR, immunoblotting, histology, euglycaemic–hyperinsulinaemic clamps and glucose tolerance tests were performed to determine the phenotypic and functional outcomes of maternal programmed miR-126-3p levels in offspring adipose tissue. Results The proteomic approach confirmed the identity of known targets of miR-126-3p (including IRS-1) and identified Lunapark, an endoplasmic reticulum (ER) protein, as a novel one. We confirmed by luciferase assay that Lunapark was a direct target of miR-126-3p. Overexpression of miR-126-3p in vitro led to a reduction in Lunapark protein levels and increased Perk (also known as Eif2ak3) mRNA levels and small interference-RNA mediated knockdown of Lunapark led to increased Xbp1, spliced Xbp1, Chop (also known as Ddit3) and Perk mRNA levels and an ER stress transcriptional response in 3T3-L1 pre-adipocytes. Consistent with the results found in vitro, increased miR-126-3p expression in adipose tissue from adult mouse offspring born to obese dams was accompanied by decreased Lunapark and IRS-1 protein levels and increased markers of ER stress. At the whole-body level the animals displayed glucose intolerance. Conclusions/interpretation Concurrently targeting IRS-1 and Lunapark, a nutritionally programmed increase in miR-126-3p causes adipose tissue insulin resistance and an ER stress response, both of which may contribute to impaired glucose tolerance. These findings provide a novel mechanism by which obesity during pregnancy leads to increased risk of type 2 diabetes in the offspring and therefore identify miR-126-3p as a potential therapeutic target. Graphical abstract


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