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

Autor(es)

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]

Afiliação do(s) autor(es)

^[1] Univ Campinas UNICAMP, Inst Biol, Obes & Comorbid Res Ctr, Rua Carl Von Linnaeus, Bloco Z, BR-13083864 Campinas, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Cellular Physiology; v. 234, n. 6, p. 9802-9809, JUN 2019.
• Citações Web of Science: 2

Resumo

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)

• Processo FAPESP: 17/06475-1 - Efeito do exercício físico sobre a modulação da expressão do receptor ativado por proliferadores de peroxissomos ³ (PPAR³) e da "insulin-degrading enzyme" (IDE) em ilhotas pancreáticas de camundongos
• Beneficiário: Mirian Ayumi Kurauti
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 15/12611-0 - Mecanismos moleculares envolvidos na disfunção e morte de células beta pancreáticas no Diabetes mellitus: estratégias para a inibição desses processos e para a recuperação da massa insular
• Beneficiário: Antonio Carlos Boschiero
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 14/24719-7 - Efeito do exercício físico sobre a modulação da expressão do receptor ativado por proliferadores de peroxissomos gama (PPARgama) e da Insulin Degrading Enzyme em ilhotas pancreáticas de camundongos
• Beneficiário: Mirian Ayumi Kurauti
• Modalidade de apoio: Bolsas no Brasil - Doutorado