Skip to main content
Erschienen in: European Journal of Nutrition 4/2018

17.03.2017 | Original Contribution

miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet

Erschienen in: European Journal of Nutrition | Ausgabe 4/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

To evaluate the role of miR-124a in the regulation of genes involved in insulin exocytosis and its effects on the kinetics of insulin secretion in pancreatic islets from pregnant rats submitted to a low-protein diet.

Methods

Adult control non-pregnant (CNP) and control pregnant (CP) rats were fed a normal protein diet (17%), whereas low-protein non-pregnant (LPNP) and low-protein pregnant (LPP) rats were fed a low-protein diet (6%) from days 1 to 15 of pregnancy. Kinetics of the glucose-induced insulin release and measurement of [Ca2+]i in pancreatic islets were assessed by standard protocols. The miR-124a expression and gene transcriptions from pancreatic islets were determined by real-time polymerase chain reaction.

Results

In islets from LPP rats, the first phase of insulin release was abrogated. The AUC [Ca2+]i from the LPP group was lower compared with the other groups. miR-124a expression was reduced by a low-protein diet. SNAP-25 mRNA, protein expression, and Rab3A protein content were lower in the LPP rats than in CP rats. Syntaxin 1A and Kir6.2 mRNA levels were decreased in islets from low-protein rats compared with control rats, whereas their protein content was reduced in islets from pregnant rats.

Conclusions

Loss of biphasic insulin secretion in islets from LPP rats appears to have resulted from reduced [Ca2+]i due, at least in part, to Kir6.2 underexpression and from the changes in exocytotic elements that are influenced either directly or indirectly by miR-124a.
Literatur
1.
Zurück zum Zitat Parsons JA, Brelje TC, Sorenson RL (1992) Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130:1459–1466PubMed Parsons JA, Brelje TC, Sorenson RL (1992) Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130:1459–1466PubMed
2.
Zurück zum Zitat Weinhaus AJ, Stout LE, Sorenson RL (1996) Glucokinase, hexokinase, glucose transporter 2, and glucose metabolism in islets during pregnancy and prolactin-treated islets in vitro: mechanisms for long term up-regulation of islets. Endocrinology 137:1640–1649CrossRefPubMed Weinhaus AJ, Stout LE, Sorenson RL (1996) Glucokinase, hexokinase, glucose transporter 2, and glucose metabolism in islets during pregnancy and prolactin-treated islets in vitro: mechanisms for long term up-regulation of islets. Endocrinology 137:1640–1649CrossRefPubMed
3.
Zurück zum Zitat Weinhaus AJ, Bhagroo NV, Brelje TC, Sorenson RL (1998) Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy. Diabetes 47:1426–1435CrossRefPubMed Weinhaus AJ, Bhagroo NV, Brelje TC, Sorenson RL (1998) Role of cAMP in upregulation of insulin secretion during the adaptation of islets of Langerhans to pregnancy. Diabetes 47:1426–1435CrossRefPubMed
4.
Zurück zum Zitat Cunha DA, Amaral ME, Carvalho CP, Collares-Buzato CB, Carneiro EM, Boschero AC (2006) Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets. Biol Res 39:555–566CrossRefPubMed Cunha DA, Amaral ME, Carvalho CP, Collares-Buzato CB, Carneiro EM, Boschero AC (2006) Increased expression of SNARE proteins and synaptotagmin IV in islets from pregnant rats and in vitro prolactin-treated neonatal islets. Biol Res 39:555–566CrossRefPubMed
5.
Zurück zum Zitat Amaral AG, Rafacho A, Machado de Oliveira CA, Batista TM, Ribeiro RA, Latorraca MQ, Bposchero AC, Carneiro EM (2010) Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice. Pancreas 39:847–855CrossRefPubMed Amaral AG, Rafacho A, Machado de Oliveira CA, Batista TM, Ribeiro RA, Latorraca MQ, Bposchero AC, Carneiro EM (2010) Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice. Pancreas 39:847–855CrossRefPubMed
6.
Zurück zum Zitat Souza DF, Ignacio-Souza LM, Reis SR, Reis MA, Stoppiglia LF, Carneiro EM, Boschero AC, Arantes VC, Latorraca MQ (2012) A low-protein diet during pregnancy alters glucose metabolism and insulin secretion. Cell Biochem Funct 30:114–121CrossRef Souza DF, Ignacio-Souza LM, Reis SR, Reis MA, Stoppiglia LF, Carneiro EM, Boschero AC, Arantes VC, Latorraca MQ (2012) A low-protein diet during pregnancy alters glucose metabolism and insulin secretion. Cell Biochem Funct 30:114–121CrossRef
7.
Zurück zum Zitat Soriano S, Gonzalez A, Marroqui L, Tuduri E, Vieira E, Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A, Carneiro EM, Quesada I (2010) Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulus-secretion coupling. Endocrinology 151:3543–3554CrossRefPubMed Soriano S, Gonzalez A, Marroqui L, Tuduri E, Vieira E, Amaral AG, Batista TM, Rafacho A, Boschero AC, Nadal A, Carneiro EM, Quesada I (2010) Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulus-secretion coupling. Endocrinology 151:3543–3554CrossRefPubMed
8.
Zurück zum Zitat Batista TM, Ribeiro RA, Silva PM, Camargo RL, Lollo PC, Boschero AC, Carneiro EM (2013) Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet. Mol Nutr Food Res 57:423–434CrossRefPubMed Batista TM, Ribeiro RA, Silva PM, Camargo RL, Lollo PC, Boschero AC, Carneiro EM (2013) Taurine supplementation improves liver glucose control in normal protein and malnourished mice fed a high-fat diet. Mol Nutr Food Res 57:423–434CrossRefPubMed
9.
Zurück zum Zitat Milanski M, Arantes VC, Ferreira F, de Barros Reis MA Carneiro EM, Boschero AC, Collares-Buzato CB, Latorraca MQ (2005) Low-protein diets reduce PKAalpha expression in islets from pregnant rats. J Nutr 135:1873–1878CrossRefPubMed Milanski M, Arantes VC, Ferreira F, de Barros Reis MA Carneiro EM, Boschero AC, Collares-Buzato CB, Latorraca MQ (2005) Low-protein diets reduce PKAalpha expression in islets from pregnant rats. J Nutr 135:1873–1878CrossRefPubMed
10.
Zurück zum Zitat Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13CrossRefPubMedPubMedCentral Sempere LF, Freemantle S, Pitha-Rowe I, Moss E, Dmitrovsky E, Ambros V (2004) Expression profiling of mammalian microRNAs uncovers a subset of brain-expressed microRNAs with possible roles in murine and human neuronal differentiation. Genome Biol 5:R13CrossRefPubMedPubMedCentral
11.
12.
Zurück zum Zitat Lovis P, Gattesco S, Regazzi R (2008) Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem 389:305–312CrossRefPubMed Lovis P, Gattesco S, Regazzi R (2008) Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs. Biol Chem 389:305–312CrossRefPubMed
13.
Zurück zum Zitat Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA, van Obberghen E (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282:19575–19588CrossRefPubMed Baroukh N, Ravier MA, Loder MK, Hill EV, Bounacer A, Scharfmann R, Rutter GA, van Obberghen E (2007) MicroRNA-124a regulates Foxa2 expression and intracellular signaling in pancreatic beta-cell lines. J Biol Chem 282:19575–19588CrossRefPubMed
14.
Zurück zum Zitat Scott AM, Atwater I, Rojas E (1981) A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia 21:470–475CrossRefPubMed Scott AM, Atwater I, Rojas E (1981) A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans. Diabetologia 21:470–475CrossRefPubMed
15.
Zurück zum Zitat Bordin S, Boschero AC, Carneiro EM, Atwater I (1995) Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists. J Membr Biol 148:177–184CrossRefPubMed Bordin S, Boschero AC, Carneiro EM, Atwater I (1995) Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists. J Membr Biol 148:177–184CrossRefPubMed
16.
Zurück zum Zitat Kelley GG, Zawalich KC, Zawalich WS (1995) Synergistic interaction of glucose and neurohumoral agonists to stimulate islet phosphoinositide hydrolysis. Am J Physiol 269:E575–E582PubMed Kelley GG, Zawalich KC, Zawalich WS (1995) Synergistic interaction of glucose and neurohumoral agonists to stimulate islet phosphoinositide hydrolysis. Am J Physiol 269:E575–E582PubMed
17.
Zurück zum Zitat Amaral ME, Ueno M, Carvalheira JB, Carneiro EM Velloso LA, Saad MJ, Boschero AC (2003) Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway. Hormon Metab Res 35:282–289CrossRef Amaral ME, Ueno M, Carvalheira JB, Carneiro EM Velloso LA, Saad MJ, Boschero AC (2003) Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway. Hormon Metab Res 35:282–289CrossRef
18.
Zurück zum Zitat Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254CrossRefPubMed
19.
Zurück zum Zitat Gutierrez JM, Alvarez J, Díaz F, Fernández S, Menéndez-Patterson A (1991) Influence of nitrogen balance and intestinal glucose absorption on growth of rats recovery from early undernutrition. Nutr Res 11:835–840CrossRef Gutierrez JM, Alvarez J, Díaz F, Fernández S, Menéndez-Patterson A (1991) Influence of nitrogen balance and intestinal glucose absorption on growth of rats recovery from early undernutrition. Nutr Res 11:835–840CrossRef
20.
Zurück zum Zitat Fernández A, Ordás I, Gutiérrez JM, Ganzález C, Fernández S, Patterson AM (1993) The rehabilitation of malnourished rat, at the end of the lactation period, with two different sources of dietary lipids: soybean and olive oils. Nutrition. 12:79–88 (Life Science Advances) Fernández A, Ordás I, Gutiérrez JM, Ganzález C, Fernández S, Patterson AM (1993) The rehabilitation of malnourished rat, at the end of the lactation period, with two different sources of dietary lipids: soybean and olive oils. Nutrition. 12:79–88 (Life Science Advances)
21.
Zurück zum Zitat Cerasi E, Luft R (1967) The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol 55:278–304CrossRef Cerasi E, Luft R (1967) The plasma insulin response to glucose infusion in healthy subjects and in diabetes mellitus. Acta Endocrinol 55:278–304CrossRef
22.
Zurück zum Zitat Henquin JC (2009) Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 52:739–751CrossRefPubMed Henquin JC (2009) Regulation of insulin secretion: a matter of phase control and amplitude modulation. Diabetologia 52:739–751CrossRefPubMed
23.
Zurück zum Zitat Rajan AS, Hill RS, Boyd AE 3rd (1989) Effect of rise in cAMP levels on Ca2 + influx through voltage-dependent Ca2+ channels in HIT cells. Second-messenger synarchy in beta-cells. Diabetes 38:874–880CrossRefPubMed Rajan AS, Hill RS, Boyd AE 3rd (1989) Effect of rise in cAMP levels on Ca2 + influx through voltage-dependent Ca2+ channels in HIT cells. Second-messenger synarchy in beta-cells. Diabetes 38:874–880CrossRefPubMed
24.
Zurück zum Zitat Nadal A, Rovira JM, Laribi O, Leon-Quinto T, Andreu E, Ripoll C, Soria B (1998) Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor. FASEB J 12:1341–1348CrossRefPubMed Nadal A, Rovira JM, Laribi O, Leon-Quinto T, Andreu E, Ripoll C, Soria B (1998) Rapid insulinotropic effect of 17beta-estradiol via a plasma membrane receptor. FASEB J 12:1341–1348CrossRefPubMed
25.
Zurück zum Zitat Rafacho A, Marroquí L, Taboga SR, Abrantes JL, Silveira LR, Boschero AC, Carneiro EM, Bosqueiro JR, Nadal A, Quesada I (2010) Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets. Endocrinology 151:85–95CrossRefPubMed Rafacho A, Marroquí L, Taboga SR, Abrantes JL, Silveira LR, Boschero AC, Carneiro EM, Bosqueiro JR, Nadal A, Quesada I (2010) Glucocorticoids in vivo induce both insulin hypersecretion and enhanced glucose sensitivity of stimulus-secretion coupling in isolated rat islets. Endocrinology 151:85–95CrossRefPubMed
26.
Zurück zum Zitat Zhang Q, Köhler M, Yang SN, Zhang F, Larsson O, Berggren PO (2004) Growth hormone promotes Ca(2+)-induced Ca2+ release in insulin-secreting cells by ryanodine receptor tyrosine phosphorylation. Mol Endocrinol 18:1658–1669CrossRefPubMed Zhang Q, Köhler M, Yang SN, Zhang F, Larsson O, Berggren PO (2004) Growth hormone promotes Ca(2+)-induced Ca2+ release in insulin-secreting cells by ryanodine receptor tyrosine phosphorylation. Mol Endocrinol 18:1658–1669CrossRefPubMed
27.
Zurück zum Zitat Straub SG, Sharp GW, Meglasson MD, de Souza CJ (2001) Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action. Biosci Rep 21:653–666CrossRefPubMed Straub SG, Sharp GW, Meglasson MD, de Souza CJ (2001) Progesterone inhibits insulin secretion by a membrane delimited, non-genomic action. Biosci Rep 21:653–666CrossRefPubMed
28.
Zurück zum Zitat Slingerland AS, Hattersley AT (2005) Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment. Ann Med 37:186–195CrossRefPubMed Slingerland AS, Hattersley AT (2005) Mutations in the Kir6.2 subunit of the KATP channel and permanent neonatal diabetes: new insights and new treatment. Ann Med 37:186–195CrossRefPubMed
29.
Zurück zum Zitat Izumi T, Gomi H, Kasai K, Mizutani S, Torii S (2003) The roles of Rab27 and its effectors in the regulated secretory pathways. Cell Struct Funct. 28:465–474.CrossRefPubMed Izumi T, Gomi H, Kasai K, Mizutani S, Torii S (2003) The roles of Rab27 and its effectors in the regulated secretory pathways. Cell Struct Funct. 28:465–474.CrossRefPubMed
30.
Zurück zum Zitat Cheviet S, Coppola T, Haynes LP, Burgoyne RD, Regazzi R (2004) The Rab-binding protein Noc2 is associated with insulin-containing secretory granules and is essential for pancreatic beta-cell exocytosis. Mol Endocrinol 18:117–126CrossRefPubMed Cheviet S, Coppola T, Haynes LP, Burgoyne RD, Regazzi R (2004) The Rab-binding protein Noc2 is associated with insulin-containing secretory granules and is essential for pancreatic beta-cell exocytosis. Mol Endocrinol 18:117–126CrossRefPubMed
31.
Zurück zum Zitat Kasai K, Ohara-Iamizumi M, Takahashi N, Mizutani S, Zhao S, Kikuta T, Kasai H, Nagamatsu S, Gomi H, Izumi T (2005) Rab27A a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation. J Clin Investig 115:388–396CrossRefPubMedPubMedCentral Kasai K, Ohara-Iamizumi M, Takahashi N, Mizutani S, Zhao S, Kikuta T, Kasai H, Nagamatsu S, Gomi H, Izumi T (2005) Rab27A a mediates the tight docking of insulin granules onto the plasma membrane during glucose stimulation. J Clin Investig 115:388–396CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Donelan MJ, Morfini G, Julyan R, Sommers S, Hays L, Kajio H, Briaud I, Easom RA, Molkentin JD, Brady ST, Rhodes CJ (2002) Ca2+-dependent dephosphorylation of kinesin heavy chain on beta-granules in pancreatic beta-cells. Implications for regulated beta-granule transport and insulin exocytosis. J Biol Chem 277:24232–24242CrossRefPubMed Donelan MJ, Morfini G, Julyan R, Sommers S, Hays L, Kajio H, Briaud I, Easom RA, Molkentin JD, Brady ST, Rhodes CJ (2002) Ca2+-dependent dephosphorylation of kinesin heavy chain on beta-granules in pancreatic beta-cells. Implications for regulated beta-granule transport and insulin exocytosis. J Biol Chem 277:24232–24242CrossRefPubMed
33.
Zurück zum Zitat Yaekura K, Julyan R, Wicksteed BL, Hays LB, Alarcon C, Sommers S, Poitout V, Baskin DG, Wang Y, Philipson LH, Rhodes CJ (2003) Insulin secretory deficiency and glucose intolerance in Rab3A null mice. J Biol Chem 278:9715–9721CrossRefPubMed Yaekura K, Julyan R, Wicksteed BL, Hays LB, Alarcon C, Sommers S, Poitout V, Baskin DG, Wang Y, Philipson LH, Rhodes CJ (2003) Insulin secretory deficiency and glucose intolerance in Rab3A null mice. J Biol Chem 278:9715–9721CrossRefPubMed
34.
Zurück zum Zitat Sudhof TC (1995) The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 375:645–653CrossRefPubMed Sudhof TC (1995) The synaptic vesicle cycle: a cascade of protein-protein interactions. Nature 375:645–653CrossRefPubMed
35.
Zurück zum Zitat Huang X, Wheeler MB, Kang YH, Sheu L, Lukacs GL, Trimble WS, Gaisano HY (1998) Truncated SNAP-25 (1–197), like botulinum neurotoxin A, can inhibit insulin secretion from HIT-T15 insulinoma cells. Mol Endocrinol 12:1060–1070PubMed Huang X, Wheeler MB, Kang YH, Sheu L, Lukacs GL, Trimble WS, Gaisano HY (1998) Truncated SNAP-25 (1–197), like botulinum neurotoxin A, can inhibit insulin secretion from HIT-T15 insulinoma cells. Mol Endocrinol 12:1060–1070PubMed
Metadaten
Titel
miR-124a expression contributes to the monophasic pattern of insulin secretion in islets from pregnant rats submitted to a low-protein diet
Publikationsdatum
17.03.2017
Erschienen in
European Journal of Nutrition / Ausgabe 4/2018
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-017-1425-z

Weitere Artikel der Ausgabe 4/2018

European Journal of Nutrition 4/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.