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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Hyperinsulinemia is associated with increasing insulin secretion but not with decreasing insulin clearance in an age-related metabolic dysfunction mice model

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Kurauti, Mirian A. [1] ; Ferreira, Sandra M. [1] ; Soares, Gabriela M. [1] ; Vettorazzi, Jean F. [1] ; Carneiro, Everardo M. [1] ; Boschero, Antonio C. [1] ; Costa-Junior, Jose M. [1]
Total Authors: 7
[1] Univ Campinas UNICAMP, Inst Biol, Obes & Comorbid Res Ctr, Rua Carl Von Linnaeus, Bloco Z, BR-13083864 Campinas, SP - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Cellular Physiology; v. 234, n. 6, p. 9802-9809, JUN 2019.
Web of Science Citations: 2

Human life expectancy is increasing faster lately and, consequently, the number of patients with age-related diseases such as type 2 diabetes (T2D) is rising every year. Cases of hyperinsulinemia have been extensively reported in elderly subjects and this alteration in blood insulin concentration is postulated to be a cause of insulin resistance, which in some cases triggers T2D onset. Thus, it is important to know the underlying mechanisms of age-dependent hyperinsulinemia to find new strategies to prevent T2D in elderly subjects. Two processes control blood insulin concentration: Insulin secretion by the endocrine portion of the pancreas and insulin clearance, which occurs mainly in the liver by the action of the insulin-degrading enzyme (IDE). Here, we demonstrated that 10-month-old mice (old) display increased body and fat pad weight, compared with 3-month-old mice (control), and these alterations were accompanied by glucose and insulin intolerance. We also confirm hyperinsulinemia in the old mice, which was related to increased insulin secretion but not to reduced insulin clearance. Although no changes in insulin clearance were observed, IDE activity was lower in the liver of old compared with the control mice. However, this decreased IDE activity was compensated by increased expression of IDE protein in the liver, thus explaining the similar insulin clearance observed in both groups. In conclusion, at the beginning of aging, 10-month-old mice do not display any alterations in insulin clearance. Therefore, hyperinsulinemia is initiated primarily due to a higher insulin secretion in the age-related metabolic dysfunction in mice. (AU)

FAPESP's process: 17/06475-1 - Effect of physical exercise on modulation of peroxisome proliferator-activated receptor ³ (PPAR³) and insulin-degrading enzyme (IDE) in the pancreatic islet of mice
Grantee:Mirian Ayumi Kurauti
Support Opportunities: Scholarships in Brazil - Post-Doctoral
FAPESP's process: 15/12611-0 - Molecular mechanisms involved in pancreatic beta cell disfunction and dead in diabetes mellitus: strategies for the inhibition of these processes and restoration of the insular mass
Grantee:Antonio Carlos Boschiero
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 14/24719-7 - Effect of physical exercise on the expression of peroxisome proliferator activated receptor gamma (PPARgamma) and Insulin Degrading Enzyme (IDE) in mouse pancreatic islets
Grantee:Mirian Ayumi Kurauti
Support Opportunities: Scholarships in Brazil - Doctorate