Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb

Kuwabara, Tomoko; Kagalwala, Mohamedi N.; Onuma, Yasuko; Ito, Yuzuru; Warashina, Masaki; Terashima, Kazuyuki; Sanosaka, Tsukasa; Nakashima, Kinichi; Gage, Fred H.; Asashima, Makoto

doi:10.1002/emmm.201100177

Cited by 114 publications

(109 citation statements)

References 56 publications

(75 reference statements)

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“…Although it is widely assumed that pancreatic insulin underlies the brain actions of this hormone (31), it is now firmly established that the brain also produces insulin (32). The same is true for IGF-I, a hormone that reaches the brain from the circulation (33) but is also locally produced (34).…”

Section: I+i Modulate Neuronal Activity: Role Of Glucose Handling By mentioning

confidence: 99%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.

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Section: I+i Modulate Neuronal Activity: Role Of Glucose Handling By mentioning

confidence: 99%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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“…Kerusakan sel beta pankreas terjadi pada saat fetus mengalami perkembangan di rahim, tepatnya pada awal terjadinya organogenesis, bersamaan dengan berkembangnya neuronal tube sebagai awal perkembangan sel saraf. 8 Pada periode ini terjadi juga ekspresi gen yang tumpang tindih secara luas, seperti ekspresi gen Pdx1, gen Nkx6. 1,9 dan ekspresi gen Ngn3, 10 dapat meyebabkan disfungsi dan kematian sel beta pankreas, bersamaan dengan sel-sel saraf penghasil insulin.…”

Section: Pendahuluanunclassified

“…1,9 dan ekspresi gen Ngn3, 10 dapat meyebabkan disfungsi dan kematian sel beta pankreas, bersamaan dengan sel-sel saraf penghasil insulin. 8 Tujuan penelitian ini ialah mempelajari kemampuan asam valproat dalam memengaruhi proses organogenesis pada fetus tikus dan dampaknya pada perkembangan selsel saraf dentate gyrus hipokampus otak yang berperan dalam sintesis insulin. …”

Section: Pendahuluanunclassified

“…Sel-sel pada daerah DG hipokampus diduga telah menyekresi insulin yang digunakan untuk regenerasi sel-sel saraf. 8 Menurut Kuwabara dkk. 8 sel-sel saraf secara terus menerus memperbaharui diri di DG dan proses ini dipromotori oleh pelepasan Wnt3 dari sel glia astrosit.…”

Section: Gambar 4 Gambaran Histopatologis Dentate Gyrus Dan Pleksus Kunclassified

“…8 Menurut Kuwabara dkk. 8 sel-sel saraf secara terus menerus memperbaharui diri di DG dan proses ini dipromotori oleh pelepasan Wnt3 dari sel glia astrosit. Pensignalan Wnt3 menginduksi ekspresi NeuroD1 (faktor transkripsi) yang berperan penting dalam perkembangan pankreas dan otak yang diperlukan untuk ekspresi gen insulin.…”

Section: Gambar 4 Gambaran Histopatologis Dentate Gyrus Dan Pleksus Kunclassified

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Pemberian Asam Valproat pada Induk Tikus Bunting Menghambat Sintesis Insulin pada Sel Otak Anak Tikus

Komariah¹,

Kiranadi²,

Winanto³

et al. 2017

mkb

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AbstrakAsam valproat memengaruhi aktivitas histone deacetylase yang berperan dalam ekspresi gen selama organogenesis. Insulin berperan dalam proliferasi dan diferensiasi sel-sel saraf dentate gyrus hipokampus. Penelitian ini bertujuan mempelajari pengaruh pemaparan asam valproat pada induk bunting terhadap ekspresi gen insulin pada dentate gyrus. Penelitian dilakukan di UPHL IPB pada bulan Mei 2015 hingga Desember 2016 dengan 84 ekor anak tikus yang dilahirkan oleh induk tikus kontrol yang diberi asam valproat 250 mg pada umur kebuntingan 10, 13, dan 16 hari digunakan untuk pengamatan kadar glukosa, insulin, DNA, RNA, dan rasio RNA/DNA serta pengamatan mikroskopis otak. Pengamatan dilakukan selang waktu empat minggu, dimulai dari umur 4 sampai 32 minggu. Anak tikus yang dilahirkan oleh induk tikus yang diberi asam valproat selama kebuntingan mempunyai kadar glukosa otak yang lebih tinggi (p<0,01) dan insulin yang lebih rendah (p<0,05). Selama periode pertumbuhan, anak tikus yang dilahirkan oleh induk tikus yang diberi asam valproat mengalami peningkatan kadar glukosa dan penurunan kadar insulin (p<0.05). Pengamatan mikroskopis sel-sel dentate gyrus menunjukkan degenerasi sel dan tidak terlihat reaksi imunoreaktif terhadap insulin, namun terjadi penurunan konsentrasi DNA, RNA, serta rasio RNA/DNA (p<0,05). Pemberian asam valproat pada induk tikus pada umur kebuntingan 10, 13, dan 16 hari memengaruhi organogenesis otak anak tikus sehingga menyebabkan kerusakan sel-sel saraf penghasil insulin otak yang ditunjukkan oleh penurunan sekresi dan kadar insulin. [MKB. 2017;49(3) Valproic Acid Administration in Pregnant Rats Inhibits Insulin Synthesis n in Brain Cells of the Offsprings AbstractValproic acid affects the activity of histone deacetylase which eventually affects gene expression during organogenesis. Insulin plays a role in regulating the proliferation and differentiation of the dentate gyrus. This experiment was designed to study the effects of valproic acid administration on the expression of insulin gene in the dentate gyrus of pregnant rats. This study was carried out at the Laboratory Animal Management Unit (UPHL) of Bogor Agricultural University from May 2015 to December 2016, with eighty four newborn rats from control rats and VA-administered rats at the age of 10, 13, and 16 days of pregnancy. The measurements were done for glucose, insulin, DNA, and RNA concentrations in dentate gyrus and to observe the microscopic condition of the brain at the ages of 4 to 32 weeks with 4 weeks interval. Rats born form mothers administered by 250 mg valproic acid during pregnancy had higher glucose concentrations (p<0.01) and lower insulin concentrations (p<0.05) in the dentate gyrus. During the post-natal growth phase, rats born from mothers administered with valproic acid had increased glucose concentrations and decreased insulin concentrations (p<0.05). Microscopic observations of the dentate gyrus showed degeneration of nerve cells with no immunoreaction to insulin was seen in dentate gyrus cells. However, the co...

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