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Insulin action on protein Phosphatase-1 activation is enhanced by the antidiabetic agent pioglitazone in cultured diabetic hepatocytes

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Insulin Action

Part of the book series: Developments in Molecular and Cellular Biochemistry ((DMCB,volume 24))

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Abstract

Effect of the antidiabetic agent pioglitazone on the insulin-mediated activation of protein Phosphatase-1 was examined in diabetic hepatocytes. Streptozotocin-induced diabetes in Sprague Dawley rats caused a significant decrease in the activation of glycogen synthase in hepatocytes isolated from these animals. There was an inverse correlation between the hyperglycemic condition and the activation of glycogen synthase in liver cells (r = 0.93, p < 0.001). Long term incubation of diabetic hepatocytes with insulin and dexamethasone caused significant (p < 0.001) improvement in the activation of glycogen synthase activation. When incubated along with hormones, pioglitazone enhanced their action (p < 0.05-0.01). Diabetic hepatocytes were also characterized by 50% decrease in the activity of protein Phosphatase-1, the enzyme which dephosphorylates and activates glycogen synthase. Pioglitazone potentiated the acute stimulatory effect of insulin on protein Phosphatase-1 in normal hepatocytes but not in diabetic hepatocytes. Long term incubation of diabetic hepatocytes with insulin ameliorated the decrease in the protein Phosphatase -1 activity in these cells. This stimulatory long-term effect of insulin was significantly (p < 0.05) enhanced by the antidiabetic agent pioglitazone. (Mol Cell Biochem 182: 185-191, 1998)

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Abbreviations

STZ:

streptozotocin

DMEM:

Dulbecco’s modified eagle medium

MAP kinase:

mitogen-activated protein kinase

MEK:

MAP kinase kinase

NIDDM:

non-insulin-dependent diabetes mellitus

PI3-kinase:

phosphatidylinositol 3-kinase

PP-1:

protein phosphatase-1

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Authors and Affiliations

  1. Department of Biochemistry, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

    Subbiah Pugazhenthi & Ramji L. Khandelwal

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  1. Subbiah Pugazhenthi
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  2. Ramji L. Khandelwal
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Editors and Affiliations

  1. Centre Hospitalier de l’Université de Montreal Pavillion Hotel Dieu, 3840, Rue Saint-Urbain, Montreal, Quebec, H2W 1T8, Canada

    Ashok K. Srivastava

  2. Polypeptide Hormone Laboratory Strathcona Anatomy & Dentistry Building, 3640 University Street, Room W3, 15, Montreal, Quebec, H3A 2B2, Canada

    Barry I. Posner

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Pugazhenthi, S., Khandelwal, R.L. (1998). Insulin action on protein Phosphatase-1 activation is enhanced by the antidiabetic agent pioglitazone in cultured diabetic hepatocytes. In: Srivastava, A.K., Posner, B.I. (eds) Insulin Action. Developments in Molecular and Cellular Biochemistry, vol 24. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-5647-3_20

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  • DOI: https://doi.org/10.1007/978-1-4615-5647-3_20

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-7584-5

  • Online ISBN: 978-1-4615-5647-3

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