Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets.
Studies were performed to obtain evidence for glyconeogenesis from pyruvate to the triose phosphates in pancreatic islets. Inability to show this evidence would be consistent with the fact that glyceraldehyde, but not pyruvate, is a potent insulin secretagogue. Synthesis of 14C-labelled glucose from 14C-labelled pyruvate could not be detected. Since this might have been due to lack of sensitivity required to measure 14C-glucose production in such a scarce tissue as islets, cDNA probes were used to estimate the relative expression of genes coding for gluconeogenic enzymes. Islets expressed pyruvate carboxylase mRNA, but even islets from rats which had been starved (a condition which induces phosphoenolpyruvate carboxykinase (PEPCK) in liver, kidney and adipose tissue) showed no PEPCK mRNA. This is consistent with our previous work showing the absence of PEPCK enzyme activity in islets. Therefore, islets can convert pyruvate to oxalacetate, but since they lack PEPCK, neither the beta nor alpha cell can convert oxalacetate to phosphoenolpyruvate and carry out glyconeogenesis. Pyruvate carboxylase mRNA was increased in islets that possessed the capacity for glucose-induced insulin release versus islets that lacked the capacity to respond to glucose, such as islets from fed rats (versus starved rats) and in islets cultured at a high concentration of glucose (versus at low glucose). Pyruvate carboxylase, therefore, must be involved in pyruvate metabolism and not glyconeogenesis in the pancreatic islet.
MacDonald
M J
MJ
Childrens Diabetes Center, University of Wisconsin Medical School, Madison.
McKenzie
D I
DI
Walker
T M
TM
Kaysen
J H
JH
D000818:Animals; D015870:Gene Expression; D005943:Gluconeogenesis / Q000235:genetics*; D006019:Glycolysis; D007515:Islets of Langerhans / Q000378:metabolism*; D010071:Oxaloacetates / Q000378:metabolism; D010728:Phosphoenolpyruvate / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics* / Q000378:metabolism; D011766:Pyruvate Carboxylase / Q000235:genetics* / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D010071:Oxaloacetates; D011773:Pyruvates; D012333:RNA, Messenger; D010728:Phosphoenolpyruvate; D019289:Pyruvic Acid; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D011766:Pyruvate Carboxylase