Research Topics
Genomes and Genes
| M J MacDonaldSummaryAffiliation: University of Wisconsin Country: USA Publications
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Detail Information
Publications
Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretionMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin, USA
Am J Physiol Endocrinol Metab 288:E1-15. 2005..Thus citrate oscillations may synchronize mitochondrial ATP production and anaplerosis with other cellular oscillations...- Immunochemical identification of coenzyme Q0-dihydrolipoamide adducts in the E2 components of the alpha-ketoglutarate and pyruvate dehydrogenase complexes partially explains the cellular toxicity of coenzyme Q0Michael J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA
J Biol Chem 279:27278-85. 2004..Ichas, F., and Bernardi, P. (1998) J. Biol. Chem. 273, 25734-25740)... - Stimulation of insulin release by glyceraldehyde may not be similar to glucoseMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, WI 53706, USA
Arch Biochem Biophys 447:118-26. 2006..Accumulation of D-lactate and 1-phosphoglycerate may explain why GA makes the beta-cell acidic. Reduction of both GA and MG by abundant beta-cell aldehyde reductases will lower the cytosolic NADPH/NADP ratio, which is normally high... - Synergistic potent insulin release by combinations of weak secretagogues in pancreatic islets and INS-1 cellsMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA
J Biol Chem 282:6043-52. 2007..The results suggest a new mechanism of insulin secretion in which anaplerosis increases short chain acyl-CoAs that have roles in insulin exocytosis... - Feasibility of pathways for transfer of acyl groups from mitochondria to the cytosol to form short chain acyl-CoAs in the pancreatic beta cellMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
J Biol Chem 282:30596-606. 2007.... - Production and export of metabolites from liver and heart mitochondria and anaplerosisMichael J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison, WI, USA
Mol Cell Biochem 258:201-10. 2004..This may reflect the multiple roles of the liver in body metabolism versus the specialized roles of the islet cell and heart... 
The role of rapid lipogenesis in insulin secretion: Insulin secretagogues acutely alter lipid composition of INS-1 832/13 cellsMichael J MacDonald
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Room 3459 Medical Science Center, 1300 University Avenue, Madison, WI 53706, USA
Arch Biochem Biophys 470:153-62. 2008..The results suggest that lipid remodeling and rapid lipogenesis from secretagogue carbon support insulin secretion...- Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretionMichael J MacDonald
Children Diabetes Center, Univesity of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Am J Physiol Cell Physiol 294:C442-50. 2008..The results suggest that, besides citrate, some of the products of anaplerosis are SC-CoAs, which may be precursors of molecules involved in insulin secretion... - Citrate oscillates in liver and pancreatic beta cell mitochondria and in INS-1 insulinoma cellsMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA
J Biol Chem 278:51894-900. 2003..Citrate oscillations may coordinate oscillations in mitochondrial energy production and anaplerosis with glycolytic oscillations, which in the beta cell are known to parallel oscillations in insulin secretion... - Mitochondrial malic enzyme (ME2) in pancreatic islets of the human, rat and mouse and clonal insulinoma cellsMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Arch Biochem Biophys 488:100-4. 2009..ME2's presence was confirmed with immunoblotting. There was no evidence that ME3 is present in these tissues... 
Anaplerosis from glucose, alpha-ketoisocaproate, and pyruvate in pancreatic islets, INS-1 cells and liver mitochondriaMichael J MacDonald
Childrens Diabetes Center, School of Medicine and Public Health, University of Wisconsin, Rm 3459 Medical Science Center, 1300 University Ave, Madison, WI 53706, USA
Mol Cell Biochem 313:195-202. 2008..This negative result is in agreement with our recent discovery that citrate is not the only carrier of acyl groups from the mitochondria to the cytosol in the beta cell and that acetoacetate can also transfer acyl carbon to the cytosol...- Studies with leucine, beta-hydroxybutyrate and ATP citrate lyase-deficient beta cells support the acetoacetate pathway of insulin secretionMichael J MacDonald
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Biochim Biophys Acta 1780:966-72. 2008..This strengthens the concept that acetoacetate-transferred acyl carbon can be converted to cytosolic SC-CoAs to stimulate insulin secretion... - Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetesM J MacDonald
Children s Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Diabetologia 52:1087-91. 2009..We sought to acquire new information about enzymes of glucose metabolism, with an emphasis on mitochondrial enzymes, by comparing pancreatic islets of type 2 diabetes patients with those of non-diabetic controls... - Differences between human and rodent pancreatic islets: low pyruvate carboxylase, atp citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic isletsMichael J MacDonald
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
J Biol Chem 286:18383-96. 2011.... - Survey of normal appearing mouse strain which lacks malic enzyme and Nad+-linked glycerol phosphate dehydrogenase: normal pancreatic beta cell function, but abnormal metabolite pattern in skeletal muscleM J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison, USA
Mol Cell Biochem 220:117-25. 2001..cGPD enzyme activity was undetectable in pancreatic islets, 0.5% of normal in liver, and 2.1% of normal in kidney and skeletal muscle. Malic enzyme activity was undetectable in these same tissues... - Oscillations in activities of enzymes in pancreatic islet subcellular fractions induced by physiological concentrations of effectorsM J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison, USA
Diabetes 46:1996-2001. 1997..If this is the case, pacemaker activity may result from complex effects distributed across multiple regulatory sites in both the cytosol and mitochondria, rather than from a single enzyme acting as a primary pacemaker... - Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in isletsM J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison
Horm Metab Res 24:158-60. 1992..Pyruvate carboxylase, therefore, must be involved in pyruvate metabolism and not glyconeogenesis in the pancreatic islet... - Enzymes in pancreatic islets that use NADP(H) as a cofactor including evidence for a plasma membrane aldehyde reductaseM Laclau
University of Wisconsin Childrens Diabetes Center, Madison, USA
Mol Cell Biochem 225:151-60. 2001..Reductases may be present in cytosol to protect the insulin cell from molecules that cause oxidative injury... - Export of metabolites from pancreatic islet mitochondria as a means to study anaplerosis in insulin secretionMichael J MacDonald
University of Wisconsin Children Daibetes Center, Madison, WI 53706, USA
Metabolism 52:993-8. 2003..The current results suggest that the reason for anaplerosis in insulin secretion is quite complex and not fully explained by current knowledge... - Sphingosine kinase 1 knockdown reduces insulin synthesis and secretion in a rat insulinoma cell lineN M Hasan
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, United States
Arch Biochem Biophys 518:23-30. 2012..The results indicate that SphK1 activity is important for insulin synthesis and secretion... - Potentiation by glucose metabolites of inositol trisphosphate-induced calcium mobilization in permeabilized rat pancreatic isletsR S Rana
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706
J Biol Chem 262:13567-70. 1987..S., Sekar, M.C., Hokin, L.E., and MacDonald, M.J. (1986) J. Biol. Chem. 261, 5237-5240)... - High activity of mitochondrial glycerol phosphate dehydrogenase in insulinomas and carcinoid and other tumors of the amine precursor uptake decarboxylation systemM J MacDonald
Department of Pediatrics, University of Wisconsin Medical School, Madison 53706
Cancer Res 50:7203-5. 1990..Whether this is the reason for the enriched activity of the glycerol phosphate dehydrogenase in certain amine precursor uptake decarboxylation system tumors is unknown... - Glucose-stimulated expressed sequence tags from rat pancreatic isletsM J MacDonald
University of Wisconsin Children s Diabetes Center, Madison 53706, USA
Mol Cell Endocrinol 123:199-204. 1996..FASEB J. 8, 777-781, 1994). Unidentified glucose responsive clones have been assigned GenBank accession numbers N55606-N55636, N65938 and N65939. The results implicate the proteins encoded by these mRNAs in insulin secretion... - The export of metabolites from mitochondria and anaplerosis in insulin secretionMichael J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison, WI 53706, USA
Biochim Biophys Acta 1619:77-88. 2003..Only fuels that can enhance anaplerosis via pyruvate or alpha-ketoglutarate can be insulin secretagogues... - Prevalence of early microalbuminuria in children with type 1 diabetes mellitusJennifer J F McVean
Department of Pediatrics University of Wisconsin School of Medicine and Public Health, Madison, WI 53792, USA
J Pediatr Endocrinol Metab 21:469-71. 2008 - Chronic reduction of the cytosolic or mitochondrial NAD(P)-malic enzyme does not affect insulin secretion in a rat insulinoma cell lineLaura J Brown
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
J Biol Chem 284:35359-67. 2009..The maintenance of robust insulin secretion after lowering expression of either one of these malic enzymes is consistent with the redundancy of pathways of pyruvate cycling and/or cytosolic NADPH production in insulinoma cells... - Factors correlating with improved A1C in children using continuous subcutaneous insulin infusionJennifer J F McVean
Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA
Diabetes Care 30:2499-500. 2007 - Histochemical evidence for pathways insulin cells use to oxidize glycolysis-derived NADHMichael J MacDonald
University of Wisconsin Childrens Diabetes Center Madison, WI, USA
Metabolism 51:318-21. 2002..The low lactate dehydrogenase and high mGPD emphasize the importance of mitochondrial hydrogen shuttles for reoxidation of glycolysis-derived NADH in insulin secretion... - Normal thyroid thermogenesis but reduced viability and adiposity in mice lacking the mitochondrial glycerol phosphate dehydrogenaseLaura J Brown
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53706, USA
J Biol Chem 277:32892-8. 2002..We conclude that, although mGPD is not essential for thyroid thermogenesis, variations in its function affect viability and adiposity in mice... - Lethal hypoglycemic ketosis and glyceroluria in mice lacking both the mitochondrial and the cytosolic glycerol phosphate dehydrogenasesLaura J Brown
Department of Pediatrics, University of Wisconsin, Madison, Wisconsin 53706, USA
J Biol Chem 277:32899-904. 2002.... - Sp/Krüppel-like transcription factors are essential for the expression of mitochondrial glycerol phosphate dehydrogenase promoter BNoaman M Hasan
The Children s Diabetes Center, The University of Wisconsin, Room 3550 Medical Science Center, 1300 University Avenue, Madison 53706, USA
Gene 296:221-34. 2002..The level of Sp1 protein was reduced by 50% in INS-1 cells chronically exposed to a high concentration of glucose. The results demonstrate that Sp/Krüppel-like factors are essential for mGPD gene expression... - The succinate mechanism of insulin releaseLeonard A Fahien
Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA
Diabetes 51:2669-76. 2002..In addition, inhibitors of HMG-CoA reductase interfere with insulin release and this inhibition can be reversed by mevalonate... - Differences between mouse and rat pancreatic islets: succinate responsiveness, malic enzyme, and anaplerosisMichael J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison, Wisconsin 53706, USA
Am J Physiol Endocrinol Metab 283:E302-10. 2002.... - Mouse lacking NAD+-linked glycerol phosphate dehydrogenase has normal pancreatic beta cell function but abnormal metabolite pattern in skeletal muscleM J MacDonald
University of Wisconsin Childrens Diabetes Center, Madison 53706, USA
Arch Biochem Biophys 384:143-53. 2000..Glycerol kinase is also absent in the pancreatic insulin cell, but this cell's function is essentially normal probably because of redundancy of NAD(H) shuttles... - Impaired anaplerosis and insulin secretion in insulinoma cells caused by small interfering RNA-mediated suppression of pyruvate carboxylaseNoaman M Hasan
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706, USA
J Biol Chem 283:28048-59. 2008.... - Glutamate is not a messenger in insulin secretionM J MacDonald
Childrens Diabetes Center, University of Wisconsin Medical School, Madison, Wisconsin, USA
J Biol Chem 275:34025-7. 2000..These experiments support the traditional idea that when insulin release is associated with flux through glutamate dehydrogenase, the flux is in the direction of alpha-ketoglutarate... - The sequence of the rat pyruvate carboxylase-encoding cDNAD A Lehn
Childrens Diabetes Center, University of Wisconsin, Madison 53706, USA
Gene 165:331-2. 1995..The rat cDNAs open reading frame encodes a protein of 1178 amino acids that is 98.6% identical (99.0% similar) to that of mouse PC and 96.0% identical (97.8% similar) to that of human PC... - Lower succinyl-CoA:3-ketoacid-CoA transferase (SCOT) and ATP citrate lyase in pancreatic islets of a rat model of type 2 diabetes: knockdown of SCOT inhibits insulin release in rat insulinoma cellsNoaman M Hasan
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA
Arch Biochem Biophys 499:62-8. 2010..The results further support work that suggests mitochondrial pathways involving SCOT which supply acetoacetate for export to the cytosol are important for insulin secretion... - Sequence of a cDNA encoding chicken vasoactive intestinal peptide (VIP)D R McFarlin
Department of Anatomy, University of Wisconsin Medical School, Madison 53706, USA
Gene 154:211-3. 1995..The region of chicken pre-proVIP homologous to the mammalian PHI region is not followed by an amidation signal. This unusual feature suggests that processing of the precursor may be different in the chicken... - Genetic association of the neuropilin-1 gene with type 1 diabetes in children: Neuropilin-1 expression in pancreatic isletsNoaman M Hasan
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, United States
Diabetes Res Clin Pract 87:e29-32. 2010..Neuropilin-1 peptides were confined to islets in human pancreas. This suggests neuropilins-1 could influence the development of some cases of T1D in children... - Beta-cell alpha-ketoglutarate hydroxylases may acutely participate in insulin secretionMichael J Fallon
Childrens Diabetes Center, University of Wisconsin School of Medicine and Public Health, Madison, WI 53706, USA
Metabolism 57:1148-54. 2008..It is possible that an increase in mitochondrially generated alpha-ketoglutarate derived from insulin secretagogue carbon and translocated to the cytosol may be part of the signal for insulin secretion... - Activation of the KATP channel-independent signaling pathway by the nonhydrolyzable analog of leucine, BCHYi Jia Liu
Dept of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853 6401, USA
Am J Physiol Endocrinol Metab 285:E380-9. 2003..The results indicate that increased flux through the TCA cycle is sufficient to activate the KATP channel-independent pathway... - Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic isletsSubhadra C Gunawardana
Dept. of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA
Am J Physiol Endocrinol Metab 287:E828-33. 2004..In conclusion, anaplerosis that enhances the supply and utilization of alpha-ketoglutarate in the tricarboxylic acid cycle appears to play an essential role in the generation of TDP... - Coenzyme q induces tau aggregation, tau filaments, and Hirano bodiesIsmael Santa-Mara
Centro de Biologia Molecular Severo Ochoa CSIC UAM, Universidad Autonoma de Madrid, Madrid, Spain
J Neuropathol Exp Neurol 67:428-34. 2008..Taken together, the in vitro models and findings in AD suggest that in the presence of ubiquinone, Hirano bodies may result from the interaction of actin and other proteins, including tau... - Insulin mutation screening in 1,044 patients with diabetes: mutations in the INS gene are a common cause of neonatal diabetes but a rare cause of diabetes diagnosed in childhood or adulthoodEmma L Edghill
Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, Exeter EX2 5DW, UK
Diabetes 57:1034-42. 2008..We aimed to determine the prevalence, genetics, and clinical phenotype of INS mutations in large cohorts of patients with neonatal diabetes and permanent diabetes diagnosed in infancy, childhood, or adulthood...