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[1]KY Lain, PM Catalano: Metabolic changes in pregnancy. Clin Obstet Gynecol 50, 938-948 (2007)
[2]NF Butte: Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71, 1256S-1261S (2000)
[3]JA Parsons, TC Brelje, RL Sorenson : Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130, 1459-1466 (1992)
[4]RL Sorenson, TC Brelje: Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 29, 301-307 (1997)
[5]C Munoz, P Lopez-Luna, E Herrera: Glucose and insulin tolerance tests in the rat on different days of gestation. Biol Neonate 68, 282-291 (1995)
[6]CG Di, R Miccoli, L Volpe, C Lencioni, PS Del: Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev 19, 259-270 (2003)
[7]RH Knopp, HJ Ruder, E Herrera, N Freinkel: Carbohydrate metabolism in pregnancy. VII. Insulin tolerance during late pregnancy in the fed and fasted rat. Acta Endocrinol (Copenh) 65, 352-360 (1970)
[8]F Broglio, E Arvat, A Benso, C Gottero, G Muccioli, M Papotti, AJ van der Lely, R Deghenghi, E Ghigo: Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 86, 5083-5086 (2001)
[9]K Dezaki, H Hosoda, M Kakei, S Hashiguchi, M Watanabe, K Kangawa, T Yada: Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 53, 3142-3151 (2004)
[10]T Yada, B Damdindorj, RS Rita, T Kurashina, A Ando, M Taguchi, M Koizumi, H Sone, M Nakata, M Kakei, K Dezaki: Ghrelin signalling in beta-cells regulates insulin secretion and blood glucose. Diabetes Obes Metab 16 Suppl 1, 111-117 (2014)
[11]A Kautzky-Willer, A Handisurya: Metabolic diseases and associated complications: sex and gender matter! Eur J Clin Invest 39, 631-648 (2009)
[12]V Iglesias-Barreira, MT Ahn, B Reusens, S Dahri, JJ Hoet, C Remacle: Pre- and postnatal low protein diet affect pancreatic islet blood flow and insulin release in adult rats. Endocrinology 137, 3797-3801 (1996)
[13]MA de-Mello, L Cury: Effects of protein-calorie malnutrition on endocrine pancreatic function in young pregnant rats. Braz J Med Biol Res 22, 791-794 (1989)
[14]MA de Mello, E Luciano, EM Carneiro, MQ Latorraca, CA Machado de Oliveira, AC Boschero: Glucose homeostasis in pregnant rats submitted to dietary protein restriction. Res Commun Mol Pathol Pharmacol 113-114, 229-246 (2003)
[15]AR Pinheiro, ID Salvucci, MB Aguila, CA Mandarim-de-Lacerda: Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats. Clin Sci (Lond) 114, 381-392 (2008)
[16]E Zambrano, PM Martinez-Samayoa, CJ Bautista, M Deas, L Guillen, GL Rodriguez-Gonzalez, C Guzman, F Larrea, PW Nathanielsz: Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 566, 225-236 (2005)
[17]H Guan, E Arany, JP van Beek, A Chamson-Reig, S Thyssen, DJ Hill, K Yang: Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats. Am J Physiol Endocrinol Metab 288, E663-E673 (2005)
[18]H Gao, DT Tanchico, U Yallampalli, MP Balakrishnan, C Yallampalli: Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet. Physiol Rep 3, 4 (2015)
[19]N Jansson, J Pettersson, A Haafiz, A Ericsson, I Palmberg, M Tranberg, V Ganapathy, TL Powell, T Jansson: Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576, 935-946 (2006)
[20]PE Lacy, M Kostianovsky: Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35-39 (1967)
[21]K Dezaki, H Hosoda, M Kakei, S Hashiguchi, M Watanabe, K Kangawa, T Yada: Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 53, 3142-3151 (2004)
[22]JD Carter, SB Dula, KL Corbin, R Wu, CS Nunemaker: A practical guide to rodent islet isolation and assessment. Biol Proced Online 11, 3-31 (2009)
[23]H Gao, DT Tanchico, U Yallampalli, MP Balakrishnan, C Yallampalli: Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet. Physiol Rep 3, 12 (2015)
[24]H Gao, S Sisley, C Yallampalli: Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy. Physiol Rep 3, 12 (2015)
[25]H Ni, WK De, P Walia, JP Chanoine: In vitro and in vivo effect of acylated and unacylated ghrelin on neonatal glucose homeostasis. Pediatr Res 67, 609-613 (2010)
[26]H Kageyama, H Funahashi, M Hirayama, F Takenoya, T Kita, S Kato, J Sakurai, EY Lee, S Inoue, Y Date, M Nakazato, K Kangawa, S Shioda: Morphological analysis of ghrelin and its receptor distribution in the rat pancreas. Regul Pept 126, 67-71 (2005)
[27]RH Rao: Chronic undernutrition may accentuate the beta cell dysfunction of type 2 diabetes. Diabetes Res Clin Pract 8, 125-130 (1990)
[28]A Marcal-Pessoa, C Bassi-Branco, CD Salvatierra, L Stoppiglia, L Ignacio-Souza, RS de Lima, R Veloso, RM de Barros, E Carneiro, A Boschero, V Arantes, M Latorraca: A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets. Biol Res 48, 3 (2015)
[29]J Rasschaert, B Reusens, S Dahri, A Sener, C Remacle, JJ Hoet, WJ Malaisse: Impaired activity of rat pancreatic islet mitochondrial glycerophosphate dehydrogenase in protein malnutrition. Endocrinology 136, 2631-2634 (1995)
[30]MQ Latorraca, EM Carneiro, MA Mello, AC Boschero: Reduced insulin secretion in response to nutrients in islets from malnourished young rats is associated with a diminished calcium uptake. J Nutr Biochem 10, 37-43 (1999)
[31]Ferreira F, Barbosa HC, Stoppiglia LF, Delghingaro-Augusto V, Pereira EA, Boschero AC, Carneiro EM 2004 Decreased insulin secretion in islets from rats fed a low protein diet is associated with a reduced PKAalpha expression. J Nutr 134, 63-67
[32]F Ferreira, E Filiputti, VC Arantes, LF Stoppiglia, EP Araujo, V Delghingaro-Augusto, MQ Latorraca, MH Toyama, AC Boschero, EM Carneiro: Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression. J Nutr 133, 695-699 (2003)
[33]MA de Mello, E Luciano, EM Carneiro, MQ Latorraca, CA Machado de Oliveira, AC Boschero: Glucose homeostasis in pregnant rats submitted to dietary protein restriction. Res Commun Mol Pathol Pharmacol 113-114, 229-246 (2003)
[34]S Gnanapavan, B Kola, SA Bustin, DG Morris, P McGee, P Fairclough, S Bhattacharya, R Carpenter, AB Grossman, M Korbonits: The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87, 2988 (2002)
[35]T Kurashina, K Dezaki, M Yoshida, RR Sukma, K Ito, M Taguchi, R Miura, M Tominaga, S Ishibashi, M Kakei, T Yada: The beta-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin. Sci Rep 5, 14041 (2015)
[36]Y Sun, M Asnicar, PK Saha, L Chan, RG Smith: Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 3, 379-386 (2006)
[37]M Damian, J Marie, JP Leyris, JA Fehrentz, P Verdie, J Martinez, JL Baneres, S Mary: High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs. J Biol Chem 287, 3630-3641 (2012)
[38]M Damian, S Mary, M Maingot, C M'Kadmi, D Gagne, JP Leyris, S Denoyelle, G Gaibelet, L Gavara, CM Garcia de Souza, D Perahia, E Trinquet, B Mouillac, S Galandrin, C Gales, JA Fehrentz, N Floquet, J Martinez, J Marie, JL Baneres: Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex. Proc Natl Acad Sci U S A 112, 1601-1606 (2015)
[39]S Park, H Jiang, H Zhang, RG Smith: Modification of ghrelin receptor signaling by somatostatin receptor-5 regulates insulin release. Proc Natl Acad Sci U S A 109, 19003-19008 (2012)
[40]B Chanclon, RM Luque, J Cordoba-Chacon, MD Gahete, AI Pozo-Salas, JP Castano, F Gracia-Navarro, AJ Martinez-Fuentes: Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions. PLoS One 8, e57834 (2013)
[41]JC Henquin, M Nenquin, MA Ravier, A Szollosi: Shortcomings of current models of glucose-induced insulin secretion. Diabetes Obes Metab 11 Suppl 4, 168-179 (2009)
[42]RN Kulkarni, JN Winnay, M Daniels, JC Bruning, SN Flier, D Hanahan, CR Kahn: Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines. J Clin Invest 104, R69-R75 (1999)
[43]L Lassance, M Haghiac, P Leahy, S Basu, J Minium, J Zhou, M Reider, PM Catalano, MS Hauguel-de: Identification of early transcriptome signatures in placenta exposed to insulin and obesity. Am J Obstet Gynecol 212, 647-11 (2015)
[44]U Hiden, E Glitzner, M Ivanisevic, J Djelmis, C Wadsack, U Lang, G Desoye: MT1-MMP expression in first-trimester placental tissue is upregulated in type 1 diabetes as a result of elevated insulin and tumor necrosis factor-alpha levels. Diabetes 57, 150-157 (2008)
[45]JD Frohlich, B Huppertz, PM Abuja, J Konig, G Desoye: Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia. Am J Pathol 180, 153-164 (2012)
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Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
Ghrelin doesn’t limit insulin release in pregnant rats fed low protein diet
1 Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston TX 77030, USA
2 Texas Children’s Hospital, Houston TX 77030, USA
3 Department of Biochemistry, Rice University, Houston TX 77030, USA
Abstract
To test the hypothesis that insulin secretion in pregnant rats fed LP diet is reduced by ghrelin signaling in pancreatic islets, we investigated plasma insulin levels, expression of ghrelin and its receptor and glucose stimulated insulin secretion (GSIS) of pancreatic islets in response to ghrelin. Plasma insulin levels were lower and ghrelin receptor abundance in islets was unaltered in LP rats. In the presence of both 2.8 and 16.7 mM glucose, GSIS was lower in LP compared to CT rats. In the presence of 2.8 mM glucose, GSIS was unaltered by ghrelin and its antagonist in both CT and LP rats. In the presence of 16.7 mM glucose, GSIS in LP rats was unchanged while in CT rats was reduced by ghrelin and reversed by ghrelin antagonist. These results indicate ghrelin signaling inhibits GSIS of pancreatic islets in pregnant rats fed CT diet, but it is blunted in pregnant rats fed LP diet and thus may not contribute to the reduction of plasma insulin and GSIS of pancreatic islets in late pregnancy.
Keywords
- Ghrelin
- Insulin
- Pancreatic Islet
- Pregnancy
- Low Protein Diet
References
- [1] KY Lain, PM Catalano: Metabolic changes in pregnancy. Clin Obstet Gynecol 50, 938-948 (2007)
- [2] NF Butte: Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr 71, 1256S-1261S (2000)
- [3] JA Parsons, TC Brelje, RL Sorenson : Adaptation of islets of Langerhans to pregnancy: increased islet cell proliferation and insulin secretion correlates with the onset of placental lactogen secretion. Endocrinology 130, 1459-1466 (1992)
- [4] RL Sorenson, TC Brelje: Adaptation of islets of Langerhans to pregnancy: beta-cell growth, enhanced insulin secretion and the role of lactogenic hormones. Horm Metab Res 29, 301-307 (1997)
- [5] C Munoz, P Lopez-Luna, E Herrera: Glucose and insulin tolerance tests in the rat on different days of gestation. Biol Neonate 68, 282-291 (1995)
- [6] CG Di, R Miccoli, L Volpe, C Lencioni, PS Del: Intermediate metabolism in normal pregnancy and in gestational diabetes. Diabetes Metab Res Rev 19, 259-270 (2003)
- [7] RH Knopp, HJ Ruder, E Herrera, N Freinkel: Carbohydrate metabolism in pregnancy. VII. Insulin tolerance during late pregnancy in the fed and fasted rat. Acta Endocrinol (Copenh) 65, 352-360 (1970)
- [8] F Broglio, E Arvat, A Benso, C Gottero, G Muccioli, M Papotti, AJ van der Lely, R Deghenghi, E Ghigo: Ghrelin, a natural GH secretagogue produced by the stomach, induces hyperglycemia and reduces insulin secretion in humans. J Clin Endocrinol Metab 86, 5083-5086 (2001)
- [9] K Dezaki, H Hosoda, M Kakei, S Hashiguchi, M Watanabe, K Kangawa, T Yada: Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 53, 3142-3151 (2004)
- [10] T Yada, B Damdindorj, RS Rita, T Kurashina, A Ando, M Taguchi, M Koizumi, H Sone, M Nakata, M Kakei, K Dezaki: Ghrelin signalling in beta-cells regulates insulin secretion and blood glucose. Diabetes Obes Metab 16 Suppl 1, 111-117 (2014)
- [11] A Kautzky-Willer, A Handisurya: Metabolic diseases and associated complications: sex and gender matter! Eur J Clin Invest 39, 631-648 (2009)
- [12] V Iglesias-Barreira, MT Ahn, B Reusens, S Dahri, JJ Hoet, C Remacle: Pre- and postnatal low protein diet affect pancreatic islet blood flow and insulin release in adult rats. Endocrinology 137, 3797-3801 (1996)
- [13] MA de-Mello, L Cury: Effects of protein-calorie malnutrition on endocrine pancreatic function in young pregnant rats. Braz J Med Biol Res 22, 791-794 (1989)
- [14] MA de Mello, E Luciano, EM Carneiro, MQ Latorraca, CA Machado de Oliveira, AC Boschero: Glucose homeostasis in pregnant rats submitted to dietary protein restriction. Res Commun Mol Pathol Pharmacol 113-114, 229-246 (2003)
- [15] AR Pinheiro, ID Salvucci, MB Aguila, CA Mandarim-de-Lacerda: Protein restriction during gestation and/or lactation causes adverse transgenerational effects on biometry and glucose metabolism in F1 and F2 progenies of rats. Clin Sci (Lond) 114, 381-392 (2008)
- [16] E Zambrano, PM Martinez-Samayoa, CJ Bautista, M Deas, L Guillen, GL Rodriguez-Gonzalez, C Guzman, F Larrea, PW Nathanielsz: Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 566, 225-236 (2005)
- [17] H Guan, E Arany, JP van Beek, A Chamson-Reig, S Thyssen, DJ Hill, K Yang: Adipose tissue gene expression profiling reveals distinct molecular pathways that define visceral adiposity in offspring of maternal protein-restricted rats. Am J Physiol Endocrinol Metab 288, E663-E673 (2005)
- [18] H Gao, DT Tanchico, U Yallampalli, MP Balakrishnan, C Yallampalli: Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet. Physiol Rep 3, 4 (2015)
- [19] N Jansson, J Pettersson, A Haafiz, A Ericsson, I Palmberg, M Tranberg, V Ganapathy, TL Powell, T Jansson: Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J Physiol 576, 935-946 (2006)
- [20] PE Lacy, M Kostianovsky: Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes 16, 35-39 (1967)
- [21] K Dezaki, H Hosoda, M Kakei, S Hashiguchi, M Watanabe, K Kangawa, T Yada: Endogenous ghrelin in pancreatic islets restricts insulin release by attenuating Ca2+ signaling in beta-cells: implication in the glycemic control in rodents. Diabetes 53, 3142-3151 (2004)
- [22] JD Carter, SB Dula, KL Corbin, R Wu, CS Nunemaker: A practical guide to rodent islet isolation and assessment. Biol Proced Online 11, 3-31 (2009)
- [23] H Gao, DT Tanchico, U Yallampalli, MP Balakrishnan, C Yallampalli: Appetite regulation is independent of the changes in ghrelin levels in pregnant rats fed low-protein diet. Physiol Rep 3, 12 (2015)
- [24] H Gao, S Sisley, C Yallampalli: Blunted hypothalamic ghrelin signaling reduces diet intake in rats fed a low-protein diet in late pregnancy. Physiol Rep 3, 12 (2015)
- [25] H Ni, WK De, P Walia, JP Chanoine: In vitro and in vivo effect of acylated and unacylated ghrelin on neonatal glucose homeostasis. Pediatr Res 67, 609-613 (2010)
- [26] H Kageyama, H Funahashi, M Hirayama, F Takenoya, T Kita, S Kato, J Sakurai, EY Lee, S Inoue, Y Date, M Nakazato, K Kangawa, S Shioda: Morphological analysis of ghrelin and its receptor distribution in the rat pancreas. Regul Pept 126, 67-71 (2005)
- [27] RH Rao: Chronic undernutrition may accentuate the beta cell dysfunction of type 2 diabetes. Diabetes Res Clin Pract 8, 125-130 (1990)
- [28] A Marcal-Pessoa, C Bassi-Branco, CD Salvatierra, L Stoppiglia, L Ignacio-Souza, RS de Lima, R Veloso, RM de Barros, E Carneiro, A Boschero, V Arantes, M Latorraca: A low-protein diet during pregnancy prevents modifications in intercellular communication proteins in rat islets. Biol Res 48, 3 (2015)
- [29] J Rasschaert, B Reusens, S Dahri, A Sener, C Remacle, JJ Hoet, WJ Malaisse: Impaired activity of rat pancreatic islet mitochondrial glycerophosphate dehydrogenase in protein malnutrition. Endocrinology 136, 2631-2634 (1995)
- [30] MQ Latorraca, EM Carneiro, MA Mello, AC Boschero: Reduced insulin secretion in response to nutrients in islets from malnourished young rats is associated with a diminished calcium uptake. J Nutr Biochem 10, 37-43 (1999)
- [31] Ferreira F, Barbosa HC, Stoppiglia LF, Delghingaro-Augusto V, Pereira EA, Boschero AC, Carneiro EM 2004 Decreased insulin secretion in islets from rats fed a low protein diet is associated with a reduced PKAalpha expression. J Nutr 134, 63-67
- [32] F Ferreira, E Filiputti, VC Arantes, LF Stoppiglia, EP Araujo, V Delghingaro-Augusto, MQ Latorraca, MH Toyama, AC Boschero, EM Carneiro: Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression. J Nutr 133, 695-699 (2003)
- [33] MA de Mello, E Luciano, EM Carneiro, MQ Latorraca, CA Machado de Oliveira, AC Boschero: Glucose homeostasis in pregnant rats submitted to dietary protein restriction. Res Commun Mol Pathol Pharmacol 113-114, 229-246 (2003)
- [34] S Gnanapavan, B Kola, SA Bustin, DG Morris, P McGee, P Fairclough, S Bhattacharya, R Carpenter, AB Grossman, M Korbonits: The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab 87, 2988 (2002)
- [35] T Kurashina, K Dezaki, M Yoshida, RR Sukma, K Ito, M Taguchi, R Miura, M Tominaga, S Ishibashi, M Kakei, T Yada: The beta-cell GHSR and downstream cAMP/TRPM2 signaling account for insulinostatic and glycemic effects of ghrelin. Sci Rep 5, 14041 (2015)
- [36] Y Sun, M Asnicar, PK Saha, L Chan, RG Smith: Ablation of ghrelin improves the diabetic but not obese phenotype of ob/ob mice. Cell Metab 3, 379-386 (2006)
- [37] M Damian, J Marie, JP Leyris, JA Fehrentz, P Verdie, J Martinez, JL Baneres, S Mary: High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs. J Biol Chem 287, 3630-3641 (2012)
- [38] M Damian, S Mary, M Maingot, C M'Kadmi, D Gagne, JP Leyris, S Denoyelle, G Gaibelet, L Gavara, CM Garcia de Souza, D Perahia, E Trinquet, B Mouillac, S Galandrin, C Gales, JA Fehrentz, N Floquet, J Martinez, J Marie, JL Baneres: Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex. Proc Natl Acad Sci U S A 112, 1601-1606 (2015)
- [39] S Park, H Jiang, H Zhang, RG Smith: Modification of ghrelin receptor signaling by somatostatin receptor-5 regulates insulin release. Proc Natl Acad Sci U S A 109, 19003-19008 (2012)
- [40] B Chanclon, RM Luque, J Cordoba-Chacon, MD Gahete, AI Pozo-Salas, JP Castano, F Gracia-Navarro, AJ Martinez-Fuentes: Role of endogenous cortistatin in the regulation of ghrelin system expression at pancreatic level under normal and obese conditions. PLoS One 8, e57834 (2013)
- [41] JC Henquin, M Nenquin, MA Ravier, A Szollosi: Shortcomings of current models of glucose-induced insulin secretion. Diabetes Obes Metab 11 Suppl 4, 168-179 (2009)
- [42] RN Kulkarni, JN Winnay, M Daniels, JC Bruning, SN Flier, D Hanahan, CR Kahn: Altered function of insulin receptor substrate-1-deficient mouse islets and cultured beta-cell lines. J Clin Invest 104, R69-R75 (1999)
- [43] L Lassance, M Haghiac, P Leahy, S Basu, J Minium, J Zhou, M Reider, PM Catalano, MS Hauguel-de: Identification of early transcriptome signatures in placenta exposed to insulin and obesity. Am J Obstet Gynecol 212, 647-11 (2015)
- [44] U Hiden, E Glitzner, M Ivanisevic, J Djelmis, C Wadsack, U Lang, G Desoye: MT1-MMP expression in first-trimester placental tissue is upregulated in type 1 diabetes as a result of elevated insulin and tumor necrosis factor-alpha levels. Diabetes 57, 150-157 (2008)
- [45] JD Frohlich, B Huppertz, PM Abuja, J Konig, G Desoye: Oxygen modulates the response of first-trimester trophoblasts to hyperglycemia. Am J Pathol 180, 153-164 (2012)
