Knockdown of ATP citrate lyase in pancreatic beta cells does not inhibit insulin secretion or glucose flux and implicates the acetoacetate pathway in insulin secretion

Molecular Metabolism

Volumn 5, Issue 10, 2016, Pages 980-987

  El Azzouny, Mahmoud ^a   Longacre, Melissa J ^b   Ansari, Israr ul H ^b   Kennedy, Robert T ^a   Burant, Charles F ^a   MacDonald, Michael J ^b  

^a UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^b UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

Author keywords

Acetoacetate pathway; Acetyl CoA; Citrate; Malonyl CoA; Mass spectrometry; Mitochondrial biosynthesis; Palmitate

Indexed keywords

2 OXOISOCAPROIC ACID C 13; 3 HYDROXY 3 METHYLGLUTARYL COENZYME A; ACETOACETIC ACID; ACYL COENZYME A; ADENOSINE TRIPHOSPHATE CITRATE SYNTHASE; CARBON; GLUCOSE; GLUCOSE C 13; HYDROXYCITRIC ACID; INSULIN; MALONYL COENZYME A; RADIOPHARMACEUTICAL AGENT; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG;

ARTICLE; CARBON METABOLISM; CELL STIMULATION; CONTROLLED STUDY; ENZYME INHIBITION; GENE SILENCING; GLUCOSE TRANSPORT; HUMAN; HUMAN CELL; INS 1 832 13 CELL LINE; INSULIN RELEASE; ISOTOPE LABELING; MASS SPECTROMETRY; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; SIGNAL TRANSDUCTION;

EID: 84992184225     PISSN: None     EISSN: 22128778     Source Type: Journal    
DOI: 10.1016/j.molmet.2016.07.011     Document Type: Article

References (23)

1. [1] Henquin, J.C., Triggering and amplifying pathways of regulation of insulin secretion by glucose. Diabetes 49 (2000), 1751–1760.
2. [2] Straub, S.G., Sharp, G.W., Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes/Metabolism Research and Reviews 18 (2002), 451–463.
3. [3] Corkey, B.E., Deeney, J.T., Yaney, G.C., Tornheim, K., Prentki, M., The role of long-chain fatty acyl-CoA esters in beta-cell signal transduction. Journal of Nutrition 130 (2000), 299S–304S.
4. [4] Farfari, S., Schulz, V., Corkey, B., Prentki, M., Glucose-regulated anaplerosis and cataplerosis in pancreatic beta-cells: possible implication of a pyruvate/citrate shuttle in insulin secretion. Diabetes 49 (2000), 718–726.
5. [5] MacDonald, M.J., Fahien, L.A., Brown, L.J., Hasan, N.M., Buss, J.D., Kendrick, M.A., Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. American Journal of Physiology. Endocrinology and Metabolism 288 (2005), E1–E15.
6. [6] Jitrapakdee, S., Wutthisathapornchai, A., Wallace, J.C., MacDonald, M.J., Regulation of insulin secretion: role of mitochondrial signalling. Diabetologia 53 (2010), 1019–1032.
7. [7] Prentki, M., Matschinsky, F., Madiraju, S.R., Metabolic signaling in fuel-induced insulin secretion. Cell Metabolism 18 (2013), 162–185.
8. [8] Flamez, D., Berger, V., Kruhoffer, M., Orntoft, T., Pipeleers, D., Schuit, F.C., Critical role for cataplerosis via citrate in glucose-regulated insulin release. Diabetes 51 (2002), 2018–2024.
9. [9] MacDonald, M.J., Longacre, M.J., Stoker, S.W., Kendrick, M., Thonpho, A., Brown, L.J., et al. Differences between human and rodent pancreatic islets: low pyruvate carboxylase, ATP citrate lyase, and pyruvate carboxylation and high glucose-stimulated acetoacetate in human pancreatic islets. Journal of Biological Chemistry 286 (2011), 18383–18396.
10. [10] Hasan, N.M., Longacre, M.J., Seed Ahmed, M., Kendrick, M.A., Gu, H., Ostenson, C.G., et al. 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 cells. Archives of Biochemistry and Biophysics 499 (2010), 62–68.
11. [11] Macdonald, M.J., Hasan, N.M., Longacre, M.J., Studies with leucine, beta-hydroxybutyrate and ATP citrate lyase-deficient beta cells support the acetoacetate pathway of insulin secretion. Biochimica et Biophysica Acta 1780 (2008), 966–972.
12. [12] MacDonald, M.J., Stoker, S.W., Hasan, N.M., Anaplerosis from glucose, alpha-ketoisocaproate, and pyruvate in pancreatic islets, INS-1 cells and liver mitochondria. Molecular and Cellular Biochemistry 313 (2008), 195–202.
13. [13] MacDonald, M.J., Longacre, M.J., Stoker, S.W., Brown, L.J., Hasan, N.M., Kendrick, M.A., Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretion. American Journal of Physiology. Cell physiology 294 (2008), C442–C450.
14. [14] MacDonald, M.J., Synergistic potent insulin release by combinations of weak secretagogues in pancreatic islets and INS-1 cells. Journal of Biological Chemistry 282 (2007), 6043–6052.
15. [15] MacDonald, M.J., Smith, A.D. 3rd, Hasan, N.M., Sabat, G., Fahien, L.A., Feasibility of pathways for transfer of acyl groups from mitochondria to the cytosol to form short chain acyl-CoAs in the pancreatic beta cell. Journal of Biological Chemistry 282 (2007), 30596–30606.
16. [16] Panten, U., Willenborg, M., Schumacher, K., Hamada, A., Ghaly, H., Rustenbeck, I., Acute metabolic amplification of insulin secretion in mouse islets is mediated by mitochondrial export of metabolites, but not by mitochondrial energy generation. Metabolism 62 (2013), 1375–1386.
17. [17] Joseph, J.W., Odegaard, M.L., Ronnebaum, S.M., Burgess, S.C., Muehlbauer, J., Sherry, A.D., et al. Normal flux through ATP-citrate lyase or fatty acid synthase is not required for glucose-stimulated insulin secretion. Journal of Biological Chemistry 282 (2007), 31592–31600.
18. [18] Hohmeier, H.E., Mulder, H., Chen, G., Henkel-Rieger, R., Prentki, M., Newgard, C.B., Isolation of INS-1-derived cell lines with robust ATP-sensitive K+ channel-dependent and -independent glucose-stimulated insulin secretion. Diabetes 49 (2000), 424–430.
19. [19] Lorenz, M.A., El Azzouny, M.A., Kennedy, R.T., Burant, C.F., Metabolome response to glucose in the beta-cell line INS-1 832/13. Journal of Biological Chemistry 288 (2013), 10923–10935.
20. [20] ElAzzouny, M.A., Evans, C.R., Burant, C.F., Kennedy, R.T., Metabolomics Analysis reveals that AICAR affects glycerolipid, ceramide and nucleotide synthesis pathways in INS-1 cells. PLoS One, 10, 2015, e0129029.
21. [21] El-Azzouny, M., Evans, C.R., Treutelaar, M.K., Kennedy, R.T., Burant, C.F., Increased glucose metabolism and glycerolipid formation by fatty acids and GPR40 receptor signaling underlies the fatty acid potentiation of insulin secretion. Journal of Biological Chemistry 289 (2014), 13575–13588.
22. [22] Cheema-Dhadli, S., Halperin, M.L., Leznoff, C.C., Inhibition of enzymes which interact with citrate by (–)hydroxycitrate and 1,2,3,-tricarboxybenzene. European Journal of Biochemistry 38 (1973), 98–102.
23. [23] Board, M., Newsholme, E., Hydroxycitrate causes altered pyruvate metabolism by tumorigenic cells. Biochemistry and Molecular Biology International 40 (1996), 1047–1056.