Suppression of Prolactin Secretion Partially Explains the Antidiabetic Effect of Bromocriptine in ob/ob Mice

Author(s):Show less -

Furigo, Isadora C. ^[1] ; Suzuki, Miriam F. ^[2] ; Oliveira, Joao E. ^[2] ; Ramos-Lobo, Angela M. ^[1] ; Teixeira, Pryscila D. S. ^[1] ; Pedroso, Joao A. ^[1] ; de Alencar, Amanda ^[1] ; Zampieri, Thais T. ^[1] ; Buonfiglio, Daniella C. ^[1] ; Quaresma, Paula G. F. ^{[1, 3]} ; Prada, Patricia O. ^[4] ; Bartolini, Paolo ^[2] ; Soares, Carlos R. J. ^[2] ; Donato, Jr., Jose ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Physiol & Biophys, BR-05508000 Sao Paulo, SP - Brazil

^[2] CNEN SP, IPEN, Biotechnol Ctr, BR-05508000 Sao Paulo, SP - Brazil

^[3] Univ Estadual Campinas, Dept Internal Med, BR-13083887 Sao Paulo, SP - Brazil

^[4] Univ Estadual Campinas, Sch Appl Sci, BR-13484350 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Endocrinology; v. 160, n. 1, p. 193-204, JAN 2019.
• Web of Science Citations: 1

Abstract

Previous studies have shown that bromocriptine mesylate (Bromo) lowers blood glucose levels in adults with type 2 diabetes mellitus; however, the mechanism of action of the antidiabetic effects of Bromo is unclear. As a dopamine receptor agonist, Bromo can alter brain dopamine activity affecting glucose control, but it also suppresses prolactin (Prl) secretion, and Prl levels modulate glucose homeostasis. Thus, the objective of the current study was to investigate whether Bromo improves insulin sensitivity via inhibition of Prl secretion. Male and female ob/ob animals (a mouse model of obesity and insulin resistance) were treated with Bromo and/or Prl. Bromo-treated ob/ob mice exhibited lower serum Prl concentration, improved glucose and insulin tolerance, and increased insulin sensitivity in the liver and skeletal muscle compared with vehicle-treated mice. Prl replacement in Bromo-treated mice normalized serum Prl concentration without inducing hyperprolactinemia. Importantly, Prl replacement partially reversed the improvements in glucose homeostasis caused by Bromo treatment. The effects of the Prl receptor antagonist G129R-hPrl on glucose homeostasis were also investigated. We found that central G129R-hPrl infusion increased insulin tolerance of male ob/ob mice. In summary, our findings indicate that part of Bromo effects on glucose homeostasis are associated with decrease in serum Prl levels. Because G129R-hPrl treatment also improved the insulin sensitivity of ob/ob mice, pharmacological compounds that inhibit Prl signaling may represent a promising therapeutic approach to control blood glucose levels in individuals with insulin resistance. (AU)

• FAPESP's process: 13/25032-2 - The role of SOCS3 in the control of hyperphagia, body weight regain and gluconeogenesis after a period of food restriction
• Grantee: João Alfredo Bolivar Pedroso
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/11752-6 - Study of leptin functions during intrauterine and childhood stages in mice
• Grantee: Angela Maria Ramos Lobo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 15/10992-6 - Investigation of metabolic programming through different approaches
• Grantee: Jose Donato Junior
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/15517-6 - Involvment of molecular factors in metabolic changes during pregnancy: role of SOCS3
• Grantee: Thais Tessari Zampieri
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/21722-4 - Mechanism of action of bromocriptine and prolactin antagonists in the treatment of Diabetes and Obesity
• Grantee: Isadora Clivatti Furigo
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/25281-3 - Effects of growth hormone on POMC, cholinergic and hypothalamic paraventricular nucleus neurons: implications for energy and glycemic metabolism control
• Grantee: Paula Gabriele Fernandes Quaresma Bergonsi
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/24345-4 - Evaluation of the potential of prolactin antagonists to the treatment of obesity and Diabetes mellitus 2
• Grantee: Carlos Roberto Jorge Soares
• Support Opportunities: Regular Research Grants