TY - JOUR
T1 - Serotonin- and Dopamine-Related Gene Expression in db/db Mice Islets and in MIN6 β -Cells Treated with Palmitate and Oleate
AU - Cataldo, L. R.
AU - Mizgier, M. L.
AU - Busso, D.
AU - Olmos, P.
AU - Galgani, J. E.
AU - Valenzuela, R.
AU - Mezzano, D.
AU - Aranda, E.
AU - Cortés, V. A.
AU - Santos, J. L.
N1 - Funding Information:
The authors acknowledge Professor Dra. D. Busso, who kindly provided the mice used in this study. J. L. Santos was supported by FONDECYT Grant 1120586. L. R. Cataldo Ph.D. program was supported by CONICYT-PCHA/Doctorado Nacional/2014-21140087
Publisher Copyright:
© 2016 L. R. Cataldo et al.
PY - 2016
Y1 - 2016
N2 - High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 β-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 β-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.
AB - High circulating nonesterified fatty acids (NEFAs) concentration, often reported in diabetes, leads to impaired glucose-stimulated insulin secretion (GSIS) through not yet well-defined mechanisms. Serotonin and dopamine might contribute to NEFA-dependent β-cell dysfunction, since extracellular signal of these monoamines decreases GSIS. Moreover, palmitate-treated β-cells may enhance the expression of the serotonin receptor Htr2c, affecting insulin secretion. Additionally, the expression of monoamine-oxidase type B (Maob) seems to be lower in islets from humans and mice with diabetes compared to nondiabetic islets, which may lead to increased monoamine concentrations. We assessed the expression of serotonin- and dopamine-related genes in islets from db/db and wild-type (WT) mice. In addition, the effect of palmitate and oleate on the expression of such genes, 5HT content, and GSIS in MIN6 β-cell was determined. Lower Maob expression was found in islets from db/db versus WT mice and in MIN6 β-cells in response to palmitate and oleate treatment compared to vehicle. Reduced 5HT content and impaired GSIS in response to palmitate (-25%; p < 0.0001) and oleate (-43%; p < 0.0001) were detected in MIN6 β-cells. In conclusion, known defects of GSIS in islets from db/db mice and MIN6 β-cells treated with NEFAs are accompanied by reduced Maob expression and reduced 5HT content.
KW - Acetylserotonin O-Methyltransferase
KW - Animals
KW - Arylalkylamine N-Acetyltransferase
KW - Catechol O-Methyltransferase
KW - Cell Line
KW - Dopa Decarboxylase
KW - Dopamine beta-Hydroxylase
KW - Dopamine Plasma Membrane Transport Proteins
KW - Insulin
KW - Insulin-Secreting Cells
KW - Islets of Langerhans
KW - Mice
KW - Monoamine Oxidase
KW - Oleic Acid
KW - Palmitic Acid
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Serotonin
KW - Serotonin Plasma Membrane Transport Proteins
KW - Transcriptome
KW - Tryptophan Hydroxylase
KW - Tyrosine 3-Monooxygenase
UR - http://www.scopus.com/inward/record.url?scp=84976519849&partnerID=8YFLogxK
U2 - 10.1155/2016/3793781
DO - 10.1155/2016/3793781
M3 - Article
C2 - 27366756
AN - SCOPUS:84976519849
SN - 2314-6745
VL - 2016
JO - Journal of Diabetes Research
JF - Journal of Diabetes Research
M1 - 3793781
ER -