Gene transcription, insulin

For PEPCK to function in gluconeogenesis, oxaloacetate produced in the pyruvate carboxylase reaction in the mitochondria, must be transported to the cytoplasm. PEPCK is not under any known allosteric control. Activity of the enzyme is regulated by hormonal control of its transcription. Glucagon stimulates transcription of the structural gene for PEPCK. Insulin inhibits transcription of the enzyme. By inhibiting PEPCK gene transcription, insulin tends to depress gluconeogenesis rates. 

Protein class Gene product Insulin effect (T or 4 in transcription rate)... 

Growth promoting effects of insulin occur via interaction of the IR with Grb-2 or SHC adaptor proteins. The cascade from Grb-2 or SHC includes ras, raf, sos and MEK, culminating in activation of the gene transcription factor MAPK. Refer again to Figure 4.21. 

The diverse effects of insulin (see p. 160) are mediated by protein kinases that mutually activate each other in the form of enzyme cascades. At the end of this chain there are kinases that influence gene transcription in the nucleus by phosphorylating target proteins, or promote the uptake of glucose and its conversion into glycogen. The signal transduction pathways involved have not yet been fully explained. They are presented here in a simplified form. 

Eizirik, D. L., Cagliero, E., Bjorklund, A., and Welsh, N. (1993). Interleukin-1-induced expression of nitric oxide synthase in insulin-producing cells is preceded by c-fos induction and depends on gene transcription and protein synthesis. FEBS Lett. 317, 62-66. 

Hughes, J. H., Colca, J. R., Easom, R. A., Turk, J., and McDaniel, M. L. (1990a). Interleukin 1 inhibits insulin secretion from isolated rat pancreatic islets by a process that requires gene transcription and mRNA translation. J. Clin. Invest. 86, 856-863. 

Conn, K. J., Rich, C. B., Jensen, D. E., Fontanilla, M. R., Bashir, M. M., Rosenbloom, J., and Foster, J. A. (1996). Insulin-like growth factor-I regulates transcription of the elastin gene through a putative retinoblastoma control element. A role for Sp3 acting as a repressor of elastin gene transcription. / Biol. Chem. 271, 28853-28860. 

Efrat, S., Surana, M. and Fleischer, N. (1991) Glucose induces insulin gene transcription in a murine pancreatic /3-cell line.J. Biol. Chem., 266, 11141-11143. 

Redmon, J.B., Towle, H.C. and Robertson, R.P. (1994) Regulation of human insulin gene transcription by glucose, epinephrine, and somatostatin. Diabetes, 43, 546-551. 

Fig. 3. Regulation of malic enzyme mRNA levels in the liver by thyroid hormone. T3 both increases malic enzyme gene transcription and malic enzyme mRNA levels (stabilization). Malic enzyme mRNA levels are also reduced by glucagon and increased by insulin at a post transcriptional level.

Qsawa, H., Sutherland, C Robey, R Printz, R and Granner, D. K. (1996). Analysis of the signaling pathway involved in the negulption of hexokinase II gene transcription by insulin / BioJ. Chem. 271,16690-16694,... 

Melloul D, Marshak S, Cerasi E. Regulation of insulin gene transcription. Diabetologia. 2002 45(3) 309-326. 

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