Abstract
Increases in plasma glucose concentration enhance the expression and activity of T-type Ca2+ channels in insulin-secreting pancreatic β-cells. The resulting elevation in T-type Ca2+ channel activity results in an elevation in the basal [Ca2+]i of β-cells. High [Ca2+]i in turn causes the internalization of L-type Ca2+ channels from cytoplasmic membrane, which contributes to glucose toxicity in β-cells. Increased activity of T-type Ca2+ channels, along with elevated [Ca2+]i, promotes low threshold exocytosis of insulin under non-stimulus conditions. Emptying immediately releasable secretory granules and internalization of L-type Ca2+ channels result in defective first phase of glucose-induced insulin secretion from the β-cells. Consequently, this defect in glucose-induced insulin secretion augments the plasma glucose concentration and slows glucose uptake by peripheral tissues. The overall effect of the glucose-T-type Ca2+ channel interaction is enhanced basal insulin levels but decreased glucose-induced insulin secretion. Thus, the T-type Ca2+ channel overexpression mechanism could play a role in the development of hyperinsulinemia and insulin resistance, which occurs during the early phase of type 2 diabetes mellitus.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alvarsson M, Sundkvist G, Lager I, Henricsson M, Berntorp K, Fernqvist-Forbes E, Steen L, Westermark G, Westmark P, Örn T, Grill V (2003) Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients. Diabetes Care 26:2231–2237
Armstrong CM, Matteson DR (1985) Two distinct populations of calcium channels in a clonal line of pituitary cells. Science 227:65–67
Ashcroft FM, Kelly RP, Smith PA (1990) Two types of Ca2+ channels in rat pancreatic β-cells. Pflugers Arch Eur J Physiol 415:504–506
Bean BP, McDonough SI (1998) Two for T. Neuron 20:825–828
Bergsten P, Grapengiesser E, Gylfe E, Tengholm A, Hellman B (1994) Synchronous oscillation of cytoplasmic Ca2+ and insulin release in glucose-stimulated pancreatic islets. J Biol Chem 269:8749–8753
Bhattacharjee A, Whitehurst RM Jr, Zhang M, Wang L, Li M (1997) T-type calcium channels facilitate insulin secretion by enhancing general excitability in the insulin-secreting β-cell line, INS-1. Endocrinology 138:3735–3740
Buisson B, Bottari SP, de Gasparo M, Gallo-Payet N, Payet MD (1992) The angiotensin AT2 receptor modulates T-type calcium current in nondifferentiated NG108-15 cells. FEBS Lett 309:161–164
Caravelli V, Marcantoni A, Comunanza V, de Luca A, Díaz J, Rorges R, Carbone E (2007) Chronic hypoxia up-regulates α1H T-type channels and low-threshold catecholamine secretion in rat chromaffin cells. J Physiol 584:149–156
Chemin J, Monteil A, Briquaire C, Richard S, Perez-Reyes E, Nargeot J, Lory P (2000) Overexpression of T-type calcium channels in HEK-293 cells increases intracellular calcium without affecting cellular proliferation. FEBS Lett 478:166–172
Chiavaroli C, Vacher P, Vecsey A, Mons N, Letari O, Pralong W, Lagnaux Y, Whelan R, Schlegel W (1991) Simultaneous monitoring of cytosolic free calcium and exocytosis at the single cell level. J Neuroendocrinol 3:253–260
Chiavaroli C, Cooper DMF, Boyajian CL, Murray-Whelan R, Demaurex N, Spiegel AM, Schlegel W (1992) Spontaneous intracellular calcium oscillations and Gsα subunit expression are inversely correlated with secretory granule content in pituitary cells. J Neuroendocrinol 4:473–481
Chow RH, Lund P-E, Löser S, Panten U, Gylfe E (1995) Coincidence of early glucose-induced depolarization with lowering of cytoplasmic Ca2+ in mouse pancreatic β-cells. J Physiol 485:607–17
Cohen CJ, McCarthy RT, Barrrett PQ, Rasmussen HR (1988) Ca channels in adrenal glomerulosa cells: K+ and angiotensin II increase T-type Ca channel current. Proc Natl Acad Sci USA 85:2412–2416
Cook DL, Satin LS, Hopkins WF (1991) Pancreatic B cells are bursting, but how? Trends Neurosci 14:411–414
Cribbs LL, Lee JH, Yang J, Satin J, Zhang Y, Daud A, Barclay J, Williamson MP, Fox M, Rees M, Perez-Reyes E (1998) Cloning and characterization of alpha1H from human heart, a member of the T-type Ca2+ channel gene family. Circ Res 83:103–109
Crunelli V, Tóth TI, Cope DW, Blethyn K, Hughes SW (2005) The ‘window’ T-type calcium current in brain dynamics of different behavioral states. J Physiol 562:121–129
Dabelea D, Hamman RF (2004) Epidemiology of type 2 diabetes mellitus. In: LeRith D, Tayler SI, Olefsky JM (eds) Type 2 diabetes mellitus: a fundamental and clinical test. Lippincott Williams & Wilkins, Philadelphia, pp 785–796
Daniel S, Noda M, Straub SG, Sharp GW (1999) Identification of the docked granule pool responsible for the first phase of glucose-stimulated insulin secretion. Diabetes 48:1686–1690
Falke LC, Gillis KD, Pressel DM, Misler S (1989) Perforated patch recording’ allows long-term monitoring of metabolite-induced electrical activity and voltage-dependent Ca2+ currents in pancreatic islet B cells. FEBS Lett 251:167–72
Furukawa T, Ito H, Nitta J, Tsujino M, Adachi S, Hiroe M, Marumo F, Sawanobori T, Hiraoka M (1992) Endothelin-1 enhances calcium entry through T-type calcium channels in cultured neonatal rat ventricular myocytes. Circ Res 71:1242–1253
Gilon P, Henquin J-C (1992) Influence of membrane potential changes on cytoplasmic Ca2+ concentration in an electrically excitable cell, the insulin-secreting pancreatic B-cell. J Biol Chem 267:20713–20720
Gilon P, Henquin J-C (1995) Distinct effects of glucose on the synchronous oscillations of insulin release and cytoplasmic Ca concentration measured simultaneously in single mouse islets. Endocrinology 136:5725–5730
Gilon P, Shepherd RM, Henquin J-C (1993) Oscillations of secretion driven by oscillation of cytoplasmic Ca2+ as evidenced in single pancreatic islets. J Biol Chem 268:22265–22268
Hopkins WF, Satin LS, Cook DL (1991) Inactivation kinetics and pharmacology distinguish two calcium currents in mouse pancreatic β-cells. J Membr Biol 119:229–239
Huang L, Bhattacharjee A, Taylor JT, Zhang M, Keyser BM, Marrero L, Li M (2004) [Ca2+]i regulated CaV1.3 translocation in insulin secreting cells. Am J Physiol 286:c213–c221
Iwashima Y, Pugh W, Depaoli AM, Takeda J, Seino S, Bell GI, Polonsky KS (1993) Expression of calcium channel mRNA in rat pancreatic islets and downregulation after glucose infusion. Diabetes 42:948–955
Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW, Neifing JL, Ward WK, Beard JC, Palmer JP (1993) Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42:1663–1672
Keyser BM, Taylor JT, Choi S-K, Lu Y, Bhattacharjee A, Huang L, Pottle J, Matrougui K, Xu Z, Li M (2014) Role of T-type Ca2+ channels in basal [Ca2+]i regulation and basal insulin secretion in rat islet cells. Curr Trend Endocrinol 7:35-44
Lee JH, Daud AN, Cribbs LL, Lacerda AE, Pereverzev A, Klöckner U, Schneider T, Perez-Reyes E (1999) Cloning and expression of a novel member of the low voltage-activated T-type calcium channel family. J Neurosci 19:1912–1921
Li M, Zhang M, Huang LP, Zhou J, Zhuang H, Taylor JT, Keyser BM, Whitehurst RM Jr (2005) T-type Ca2+ channels are involved in high glucose-induced rat neonatal cardiomyocyte proliferation. Pediatr Res 57:550–556
Longo EA, Tornheim K, Deeney JT, Varnum BA, Tilostson D, Prentki M, Corkey BE (1991) Oscillation in cytosolic free Ca2+, oxygen consumption, and insulin secretion in glucose-stimulated rat pancreatic islets. J Biol Chem 266:9314–9319
Lu Y, Long M, Zhou S, Xu Z, Hu F, Li M (2014) Mibefradil reduces blood glucose concentration in db/db mice. Clinics 69:61–67
Meissner HP, Presissler M (1980) Ionic mechanisms of the glucose-induced membrane potential changes in B-cells. Horm Metab Res Suppl 10:91–99
Meissner HP, Schmelz H (1974) Membrane potential of beta-cells in pancreatic islets. Pflügers Arch 351:195–206
Michels G, Er F, Eicks M, Herzig S, Hoppe UC (2006) Long-term and immediate effect of testosterone on single T-type calcium channel in neonatal rat cardiomyocytes. Endocrinology 147:5160–5169
Misler S, Barnett BW, Gillis KD, Pressel DM (1992a) Electrophysiology of stimulus-secretion coupling in human β-cells. Diabetes 41:1221–1228
Misler S, Barnett DW, Pressel DM, Gillis KD, Scharp DW, Falke LC (1992b) Stimulus-secretion coupling in β-cells of transplantable human islets of Langerhans. Diabetes 41:662–670
Monteil A, Chemin J, Bourinet E, Mennessier G, Perez-Reyes E, Lory P, Nargeot J (2000) Molecular and functional properties of the human α1G subunit that form T-type calcium channels. J Biol Chem 275:6090–6100
Perez-Reyes E, Cribbs LL, Daud A, Lacerda AE, Barclay J, Williamson MP, Fox M, Rees M, Lee JH (1998) Molecular characterization of a neuronal low-voltage-activated T-type calcium channel. Nature 391:896–900
Pfeifer MA, Hater JB, Porte D Jr (1981) Insulin secretion in diabetes mellitus. Am J Med 70:579–588
Porte D Jr (1991) β-cells in type II diabetes mellitus. Diabetes 40:166–180
Reaven GM (2005) The insulin resistance syndrome: definition and dietary approaches to treatment. Annu Rev Nutr 25:391–406
Ritchie AK (1993) Estrogen increases low voltage-activated calcium current density in GH3 anterior pituitary cells. Endocrinology 132:1621–1629
Roe MW, Worley JF III, Tokuyama Y, Phillipson LH, Sturis J, Tang J, Dukes ID, Bell GI, Polonsky KS (1996) NIDDM is associated with loss of pancreatic β-cell L-type Ca2+ channel activity. Am J Physiol Endocrinol Metab 270:E133–E140
Rossier MF, Lesouhaitier O, Perrier E, Bockhorn L, Chiappe A, Lalevée N (2003) Aldosterone regulation of T-type calcium channels. J Steroid Biochem Mol Biol 85:383–388
Sala S, Matteson DR (1990) Single-channel recording of two types of Ca2+ channels in rat pancreatic β-cells. Biophys J 58:567–571
Scarlett JA, Griffin GJ, Olefsky JM, Kolterman OG (1982) Insulin treatment reverses the insulin resistance of type II diabetes mellitus. Diabetes Care 5:353–363
Schneggenburger R, Neher E (2000) Intracellular calcium dependence of transmitter release rates at a fast central synapse. Nature 406:889–893
Seltzer HS, Allen EW, Herron AL Jr, Brennan MT (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46:323–335
Soria B, Tudurí E, González A, Hmadcha A, Martin F, Nadal A, Quesada I (2010) Pancreatic islet cells: a model for calcium-dependent peptide release. HFSP J 4:52–60
Straub SG, Sharp GWG (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 18:451–63
Taylor JT, Huang L, Keyser BM, Zhuang H, Clarkson CW, Li M (2005) Role of high-voltage-activated calcium channels in glucose-regulated β-cell calcium homeostasis and insulin release. Am J Physiol Endocrinol Metab 289:E900–E908
Trombetta M, Boselli L, Cretti A, Cali A, Vettor M, Caruso B, Dorizzi R, Avogaro A, Muggeo M, Bonora E, Bonadonna RC (2013) Type 2 diabetes mellitus: a disease of the governance of the glucose-insulin system: an experimental metabolic control analysis study. Nutr Metab Cardiovasc Dis 23:23–30
Tsien RW, Clozel J-P, Nargeot J (1998) Low-voltage-activated T-type Ca2+ channels. Adis International Ltd, Chester, England, pp 1–394
Turner RC, Holman RR, Matthews D, Hockaday TDR, Peto J (1979) Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations. Metabology 28:1086–1096
Ullrich S, Abel K-B, Lehr S, Greger R (1996) Effects of glucose, forskolin and tolbutamide on membrane potential and insulin secretion in the insulin secreting cell line INS-1. Pflügers Arch 432:630–636
Verma S, Bhanot S, Hicke A, McNeil JH (1997) Chronic T-type Ca2+ channel blockade with mibefradil in hyperinsulinemic, insulin-resistant and hypertensive rats. Cardiovasc Res 34:121–128
Wang Z, Estacion M, Mordan LJ (1993) Ca2+ influx via T-type channels modulates PDGF-induced replication of mouse fibroblasts. Am J Physiol 265:C1239–C1246
Wang L, Bhattacharjee A, Zuo Z, Hu F, Honkanen RE, Berggren P-O, Li M (1999) A low voltage-activated Ca2+ current mediates cytokine-induced pancreatic β-cell death. Endocrinology 140:1200–1204
Weir GC, Leahy JL (1994) Pathogenesis of noninsulin dependent (type II) diabetes mellitus. In: Kahn GR, Weir GC (eds) Joslin’s diabetes mellitus. Lea & Febiger/Waverly, Philadelphia, pp 240–64
Weiss N, Zamponi GW (2013) Control of low-threshold exocytosis by T-type calcium channels. Biochim Biophys Acta 1828:1579–1586
Weiss N, Hameed S, Fernández-Fernández JM, Fablet K, Karmazinova M, Poillot C, Proft J, Chen L, Bidaud I, Monteil A, Huc-Brandt S, Lacinova L, Lory P, Zamponi GW, Michel De Waard M (2012) A Cav3.2/syntaxin-1A signaling complex controls T-type channel activity and low-threshold exocytosis. J Biol Chem 287:2810–2818
Yang SN, Berggren P-O (2005) β-Cell CaV channel regulation in physiology and pathophysiology. Am J Physiol Endocrinol Metab 288:E16–E28
Zeng X, Keyser B, Li M, Sikka SC (2005) T-type (α1G) low voltage-activated calcium channel interactions with nitric oxide-cyclic guanosine monophosphate pathway and regulation of calcium homeostasis in human cavernosal cells. J Sex Med 2:620–633
Zhang M, Zhuang H, Bhattacharjee A, Li M (2000) High glucose elevated T-type calcium channel expression and basal [Ca2+]i in rat islet beta cells. Biophys J 78:69A
Zhuang H, Bhattacharjee A, Hu F, Zhang M, Gosmami T, Wang L, Wu S, Berggren P-O, Li M (2000) Cloning of a T-type Ca2+ channel isoform in insulin-secreting cells. Diabetes 49:59–64
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer-Verlag Wien
About this chapter
Cite this chapter
Li, M. (2015). Role of T-Type Ca2+ Channels in Basal Insulin Release. In: Schaffer, S., Li, M. (eds) T-type Calcium Channels in Basic and Clinical Science. Springer, Vienna. https://doi.org/10.1007/978-3-7091-1413-1_10
Download citation
DOI: https://doi.org/10.1007/978-3-7091-1413-1_10
Published:
Publisher Name: Springer, Vienna
Print ISBN: 978-3-7091-1412-4
Online ISBN: 978-3-7091-1413-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)