Skip to main content
SpringerLink
Log in

KATP Channel-Independent Pathway and the Glucoreceptor

  • Chapter
  • First Online:
Glucose-sensing Receptor in Pancreatic Beta-cells

  • 386 Accesses

Abstract

The biphasic response is a unique characteristic of glucose-stimulated insulin secretion by islet beta cells. Namely, upon exposure to a high concentration of glucose, insulin secretion increases sharply for approximately 5 min before it gradually wanes at the end of the first phase. The second phase is characterized by sustained insulin release that lasts for the entire duration of high extracellular glucose concentration. Recently, new insights into the mechanisms underlying this phenomenon have been gained due to molecular identification of beta cell glucoreceptors. It has been previously postulated that elevation in cytosolic calcium leading to the first phase of insulin secretion is solely due to membrane depolarization caused by the closure of ATP-sensitive potassium (KATP) channels. However, the rapid increase in intracellular calcium is also caused by glucoreceptor-down signaling. Therefore, the first phase of glucose-induced secretion, i.e., fusion of the beta granule and the plasma membrane, likely arises from both glucose-receptor binding and closure of KATP channels. The molecular nature of the so-called KATP-independent glucose action appears to be diverse and still remains elusive. The releasable pool of beta granules is replenished by this glucose action, leading to the second phase of insulin secretion; signals for this phase also involve the direct recognition of glucose molecules by specific receptors. In this chapter, we review data pertaining to the functions of glucoreceptors in relation to KATP-independent glucose action in beta cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matschinsky FM, Landgraf R, Ellerman J, Kotler-Brajtburg J. Glucoreceptor mechanisms in islets of Langerhans. Diabetes. 1972;21(Suppl 2):555–69.

    Article  CAS  Google Scholar 

  2. Matschinsky FM, Pagliara AS, Hover BA, Haymond MW, Stillings SN. Differential effects of alpha- and beta-D- glucose on insulin and glucagon secretion from the isolated perfused rat pancreas. Diabetes. 1975;24:369–72.

    Article  CAS  Google Scholar 

  3. Ashcroft SJH, Bassett JM, Randle PJ. Insulin secretion mechanisms and glucose metabolism in isolated islets. Diabetes. 1972;21(Suppl 2):538–45.

    Article  CAS  Google Scholar 

  4. Niki A, Niki H, Miwa I, Okuda J. Insulin secretion by anomers of D-glucose. Science. 1974;186:150–1.

    Article  CAS  Google Scholar 

  5. Bedoya FJ, Wilson JM, Ghosh AK, Finegold D, Matschinsky FM. The glucokinase glucose sensor in human pancreatic islet tissue. Diabetes. 1986;35:61–7.

    Article  CAS  Google Scholar 

  6. Malaisse WJ, Sener A. Glucokinase is not the pancreatic B-cell glucoreceptor. Diabetologia. 1985;28:520–7.

    Article  CAS  Google Scholar 

  7. Maechler P, Kennedy ED, Pozzan T, Wollheim CB. Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic beta-cells. EMBO J. 1997;16:3833–41.

    Article  CAS  Google Scholar 

  8. Sato Y, Aizawa T, Komatsu M, Okada N, Yamada T. Dual functional role of membrane depolarization/Ca2+ influx in rat pancreatic B-cell. Diabetes. 1992;41:438–43.

    Article  CAS  Google Scholar 

  9. Aizawa T, Sato Y, Komatsu M, Hashizume K. ATP-sensitive K+ channel-independent, insulinotropic action of glucose in the B-cells. Endocr Regul. 1992;26:159–62.

    CAS  PubMed  Google Scholar 

  10. Gembal M, Gilon P, Henquin JC. Evidence that glucose can control insulin release independently from its action on ATP-sensitive K+ channels in mouse B cells. J Clin Invest. 1992;89:1288–95.

    Article  CAS  Google Scholar 

  11. Kojima I, Nakagawa Y, Hamano K, Medina J, Li L, Nagasawa M. Glucose-sensing receptor T1R3: a new signaling receptor activated by glucose in pancreatic β-cells. Biol Pharm Bull. 2015;38:674–9.

    Article  CAS  Google Scholar 

  12. Nakagawa Y, Ohtsu Y, Nagasawa M, Shibata H, Kojima I. Glucose promotes its own metabolism by acting on the cell-surface glucose-sensing receptor T1R3. Endocr J. 2014;61:119–31.

    Article  CAS  Google Scholar 

  13. Hamano K, Nakagawa Y, Ohtsu Y, Li L, Medina J, Tanaka Y, Masuda K, Komatsu M, Kojima I. Lactisole inhibits the glucose-sensing receptor T1R3 expressed in mouse pancreatic β-cells. J Endocrinol. 2015;226:57–66.

    Article  CAS  Google Scholar 

  14. Prentki M, Matschinsky FM, Madiraju SR. Metabolic signaling in fuel-induced insulin secretion. Cell Metab. 2013;18:162–85.

    Article  CAS  Google Scholar 

  15. Nagamatsu S, Ohara-Imaizumi M. Imaging exocytosis of single insulin secretory granules with TIRF microscopy. Methods Mol Biol. 2008;440:259–68.

    Article  CAS  Google Scholar 

  16. Aizawa T, Komatsu M. Rab27a: a new face in beta cell metabolism-secretion coupling. J Clin Invest. 2005;115:227–30.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Gaisano HY. Here come the newcomer granules, better late than never. Trends Endocrinol Metab. 2014;25(8):381.

    Article  CAS  Google Scholar 

  18. Dean PM, Matthews EK. Electrical activity in pancreatic islet cells. Nature. 1968;219:389–90.

    Article  CAS  Google Scholar 

  19. Straub SG, Sharp GW. Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev. 2002;18:451–63.

    Article  CAS  Google Scholar 

  20. Devis G, Somers G, Malaisse WJ. Dynamics of calcium-induced insulin release. Diabetologia. 1977;13:531–6.

    Article  CAS  Google Scholar 

  21. Grodsky GM. Threshold distribution hypothesis for packet storage of insulin. II. Effect of calcium. Diabetes. 1972;21(Suppl 2):584–93.

    Article  CAS  Google Scholar 

  22. Bolaffi JL, Heldt A, Lewis LD, Grodsky GM. The third phase of in vitro insulin secretion: evidence for glucose insensitivity. Diabetes. 1986;35:370–21.

    Article  CAS  Google Scholar 

  23. MacDonald MJ. Differences between mouse and rat pancreatic islets: succinate responsiveness, malic enzyme, and anaplerosis. Am J Physiol Endocrinol Metab. 2002;283:E302–10.

    Article  CAS  Google Scholar 

  24. Henquin JC. The dual control of insulin secretion by glucose involves triggering and amplifying pathways in β-cells. Diabetes Res Clin Pract. 2011;93(Suppl 1):S27–31.

    Article  CAS  Google Scholar 

  25. Kaminski MT, Lenzen S, Baltrusch S. Real-time analysis of intracellular glucose and calcium in pancreatic beta cells by fluorescence microscopy. Biochim Biophys Acta. 2012;1823:1697–707.

    Article  CAS  Google Scholar 

  26. Taguchi N, Aizawa T, Sato Y, Ishihara F, Hashizume K. Mechanism of glucose-induced biphasic insulin release: physiological role of adenosine triphosphate-sensitive K+ channel-independent glucose action. Endocrinology. 1995;136:3942–8.

    Article  CAS  Google Scholar 

  27. Yamada S, Komatsu M, Aizawa T, Sato Y, Yajima H, Yada T, Hashiguchi S, Yamauchi K, Hashizume K. Time-dependent potentiation of the beta cell, a Ca2+-independent phenomenon. J Endocrinol. 2002;172:345–54.

    Article  CAS  Google Scholar 

  28. Yamada S, Komatsu M, Sato Y, Yamauchi K, Kojima I, Aizawa T, Hashizume K. Time-dependent stimulation of insulin exocytosis by 3′,5′-cyclic adenosine monophosphate in the rat islet beta-cell. Endocrinology. 2002;143:4203–9.

    Article  CAS  Google Scholar 

  29. Niki I, Tamagawa T, Niki H, Niki A, Koide T, Sakamoto N. Possible involvement of diacylglycerol-activated, Ca2+-dependent protein kinase in glucose memory of the rat pancreatic B-cell. Acta Endocrinol. 1988;118:204–8.

    Article  CAS  Google Scholar 

  30. Grill V, Adamson U, Rundfeldt M, Andersson S, Cerasi E. Glucose memory of pancreatic B and A2 cells evidence for common time-dependent actions of glucose on insulin and glucagon secretion in the perfused rat pancreas. J Clin Invest. 1979;64:700–7.

    Article  CAS  Google Scholar 

  31. Aizawa T, Sato Y, Ishihara F, Komatsu M, Taguchi N, Hashizume K, Yamada T. ATP-sensitive K+ channel-independent glucose action in rat pancreatic s-cell. Am J Phys. 1994;266:C622–7.

    Article  CAS  Google Scholar 

  32. Ishihara F, Aizawa T, Taguchi N, Sato Y, Hashizume K. Differential metabolic requirement for initiation and augmentation of insulin release by glucose: a study with rat pancreatic islets. J Endocrinol. 1994;143:497–503.

    Article  CAS  Google Scholar 

  33. Komatsu M, Schermerhorn T, Aizawa T, Sharp GWG. Glucose stimulation of insulin release in the absence of extracellular Ca2+ and in the absence of any rise in intracellular Ca2+ in rat pancreatic islets. Proc Natl Acad Sci U S A. 1995;92:10728–32.

    Article  CAS  Google Scholar 

  34. Aizawa T, Kaneko T, Yajima H, Yamada S, Sato Y, Kanda Y, Kanda S, Noda M, Kadowaki T, Nagai M, Yamauchi K, Komatsu M, Hashizume K. Rapid oscillation of insulin release by the rat pancreatic islets under stringent Ca2+-free conditions. J Endocrinol. 2000;166:545–51.

    Article  CAS  Google Scholar 

  35. Denton RM. Regulation of mitochondrial dehydrogenases by calcium ions. Biochim Biophys Acta. 2009;1787:1309–16.

    Article  CAS  Google Scholar 

  36. Westerlund J, Ortsäter H, Palm F, Sundsten T, Bergsten P. Glucose-regulated pulsatile insulin release from mouse islets via the K(ATP) channel-independent pathway. Eur J Endocrinol. 2001;144:667–75.

    Article  CAS  Google Scholar 

  37. Grimberg A, Ferry RJ, Jr KA, Koo-McCoy S, Polonsky K, Glaser B, Permutt MA, Aguilar-Bryan L, Stafford D, Thornton PS, Baker L, Stanley CA. Dysregulation of insulin secretion in children with congenital hyperinsulinism due to sulfonylurea receptor mutations. Diabetes. 2001;50:322–8.

    Article  CAS  Google Scholar 

  38. Ward WK, Bolgiano DC, McKnight B, Halter JB, Porte D Jr. Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest. 1984;74:1318–28.

    Article  CAS  Google Scholar 

  39. Straub SG, Cosgrove KE, Ammälä C, Shepherd RM, O’Brien RE, Barnes PD, Kuchinski N, Chapman JC, Schaeppi M, Glaser B, Lindley KJ, Sharp GW, Aynsley-Green A, Dunne MJ. Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways. Diabetes. 2001;50:329–39.

    Article  CAS  Google Scholar 

  40. Soliman AT, Alsalmi I, Darwish A, Asfour MG. Growth and endocrine function after near total pancreatectomy for hyperinsulinaemic hypoglycaemia. Arch Dis Child. 1996;74:379–85.

    Article  CAS  Google Scholar 

  41. Ismail D, Werther G. Persistent hyperinsulinaemic hypoglycaemia of infancy: 15 years’ experience at the Royal Children’s Hospital (RCH), Melbourne. J Pediatr Endocrinol Metab. 2005;18:1103–9.

    Article  Google Scholar 

  42. Tyrrell VJ, Ambler GR, Yeow WH, Cowell CT, Silink M. Ten years’ experience of persistent hyperinsulinaemic hypoglycaemia of infancy. J Paediatr Child Health. 2001;37:483–8.

    Article  CAS  Google Scholar 

  43. Miki T, Nagashima H, Tashiro F, Kotake K, Yoshitomi H, Tamamoto A, Gonoi T, Iwanaga T, Miyazaki JI, Seino S. Defective insulin secretion and enhanced insulin action in KATP channel-deficient mice. Proc Natl Acad Sci U S A. 1998;95:10402–6.

    Article  CAS  Google Scholar 

  44. Seghers V, Nakazaki M, DeMayo F, Aguilar-Bryan L, Bryan J. Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion. J Biol Chem. 2000;31(275):9270–7.

    Article  Google Scholar 

  45. Nenquin M, Szollosi A, Aguilar-Bryan L, Bryan J, Henquin JC. Both triggering and amplifying pathways contribute to fuel-induced insulin secretion in the absence of sulfonylurea receptor-1 in pancreatic beta-cells. J Biol Chem. 2004;279:32316–24.

    Article  CAS  Google Scholar 

  46. Inagaki N, Gonoi T, Clement JP 4th, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J. Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science. 1995;270:1166–70.

    Article  CAS  Google Scholar 

  47. Shiota C, Larsson O, Shelton KD, Shiota M, Efanov AM, Hoy M, Lindner J, Kooptiwut S, Juntti-Berggren L, Gromada J, Berggren PO, Magnuson MA. Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose. J Biol Chem. 2002;277:37176–83.

    Article  CAS  Google Scholar 

  48. Ferdaoussi M, MacDonald PE. Toward connecting metabolism to the exocytotic site. Trends Cell Biol. 2017;27:163–71.

    Article  CAS  Google Scholar 

  49. Kalwat MA, Cobb MH. Mechanisms of the amplifying pathway of insulin secretion in the β cell. Pharmacol Ther. 2017;179:17–30. [Epub ahead of print]

    Article  CAS  Google Scholar 

  50. Komatsu M, Aizawa T, Yokokawa N, Sato Y, Okada N, Takasu N, Yamada T. Mastoparan-induced hormone release from rat pancreatic islets. Endocrinology. 1992;130:221–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Diabetes Center, Aizawa Hospital, Honjo, Matsumoto, Japan

    Toru Aizawa

  2. Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Shinshu University School of Medicine, Matsumoto, Japan

    Mitsuhisa Komatsu

Authors
  1. Toru Aizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mitsuhisa Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Toru Aizawa .

Editor information

Editors and Affiliations

  1. Institute for Molecular & Cellular Regulation, Gunma University, Maebashi, Gunma, Japan

    Itaru Kojima

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Aizawa, T., Komatsu, M. (2018). KATP Channel-Independent Pathway and the Glucoreceptor. In: Kojima, I. (eds) Glucose-sensing Receptor in Pancreatic Beta-cells. Springer, Singapore. https://doi.org/10.1007/978-981-13-0002-8_3

Download citation

Publish with us

Policies and ethics

Search

Navigation