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Cholinergic-pathway-weakness-associated pancreatic islet dysfunction: a low-protein-diet imprint effect on weaned rat offspring

Part of: DOHaD Research in Latin-American

Published online by Cambridge University Press:  06 April 2020

Paulo Cezar de Freitas Mathias Open the ORCID record for Paulo Cezar de Freitas Mathias [Opens in a new window] ,
Ginislene Dias Souza Miranda Open the ORCID record for Ginislene Dias Souza Miranda [Opens in a new window] ,
Luiz Felipe Barella Open the ORCID record for Luiz Felipe Barella [Opens in a new window] ,
Rosiane Aparecida Miranda Open the ORCID record for Rosiane Aparecida Miranda [Opens in a new window] ,
Audrei Pavanello Open the ORCID record for Audrei Pavanello [Opens in a new window] ,
Isabela Peixoto Martins Open the ORCID record for Isabela Peixoto Martins [Opens in a new window] ,
Júlia Cristina Facchi Open the ORCID record for Júlia Cristina Facchi [Opens in a new window] ,
Hercules de Oliveira Costermani Open the ORCID record for Hercules de Oliveira Costermani [Opens in a new window] ,
Thalyne Aparecida Leite de Lima Open the ORCID record for Thalyne Aparecida Leite de Lima [Opens in a new window]  and
Júlio Cezar de Oliveira Open the ORCID record for Júlio Cezar de Oliveira [Opens in a new window]
Paulo Cezar de Freitas Mathias
Affiliation:
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil
Ginislene Dias Souza Miranda
Affiliation:
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop, MT, Brazil
Luiz Felipe Barella
Affiliation:
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil
Rosiane Aparecida Miranda
Affiliation:
Laboratory of Endocrine Physiology, Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Audrei Pavanello
Affiliation:
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil
Isabela Peixoto Martins
Affiliation:
Laboratory of Secretion Cell Biology, Department of Biotechnology, Genetics and Cell Biology, State University of Maringá, Maringá, PR, Brazil
Júlia Cristina Facchi
Affiliation:
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop, MT, Brazil
Hercules de Oliveira Costermani
Affiliation:
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop, MT, Brazil
Thalyne Aparecida Leite de Lima
Affiliation:
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop, MT, Brazil
Júlio Cezar de Oliveira*
Affiliation:
Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Sinop, MT, Brazil
*
Address for correspondence: Júlio Cezar de Oliveira, Research Group on Perinatal Programming of Metabolic Diseases: DOHaD paradigm, Laboratory of Metabolic and Cardiovascular Diseases, Health Education and Research Center (NUPADS), room 03, Institute of Health Sciences, Federal University of Mato Grosso, University Campus of Sinop, Alexandre Ferronato Avenue 1200, 78557-267, Sinop, MT, Brazil. Email: biojborges@gmail.com
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Abstract

Currently, metabolic disorders are one of the major health problems worldwide, which have been shown to be related to perinatal nutritional insults, and the autonomic nervous system and endocrine pancreas are pivotal targets of the malprogramming of metabolic function. We aimed to assess glucose–insulin homeostasis and the involvement of cholinergic responsiveness (vagus nerve activity and insulinotropic muscarinic response) in pancreatic islet capacity to secrete insulin in weaned rat offspring whose mothers were undernourished in the first 2 weeks of the suckling phase. At delivery, dams were fed a low-protein (4% protein, LP group) or a normal-protein diet (20.5% protein, NP group) during the first 2 weeks of the suckling period. Litter size was adjusted to six pups per mother, and rats were weaned at 21 days old. Weaned LP rats presented a lean phenotype (P < 0.01); hypoglycaemia, hypoinsulinaemia and hypoleptinaemia (P < 0.05); and normal corticosteronaemia (P > 0.05). In addition, milk insulin levels in mothers of the LP rats were twofold higher than those of mothers of the NP rats (P < 0.001). Regarding glucose–insulin homeostasis, weaned LP rats were glucose-intolerant (P < 0.01) and displayed impaired pancreatic islet insulinotropic function (P < 0.05). The M3 subtype of the muscarinic acetylcholine receptor (M3mAChR) from weaned LP rats was less responsive, and the superior vagus nerve electrical activity was reduced by 30% (P < 0.01). A low-protein diet in the suckling period malprogrammes the vagus nerve to low tonus and impairs muscarinic response in the pancreatic β-cells of weaned rats, which are imprinted to secrete inadequate insulin amounts from an early age.

Keywords

Perinatal undernutritionmuscarinic receptorvagus nerveinsulin secretionpancreatic islets
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 11 , Issue 5 , October 2020 , pp. 484 - 491
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2020

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