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The imidazoline NNC77-0020 affects glucose-dependent insulin, glucagon and somatostatin secretion in mouse pancreatic islets


, : The imidazoline NNC77-0020 affects glucose-dependent insulin, glucagon and somatostatin secretion in mouse pancreatic islets. Naunyn-Schmiedeberg's Archives of Pharmacology 368(4): 284-293

The effect of the novel imidazoline compound 2-[2-(4,5-dihydro-1H-imidazol-2-yl)-1-(5-methyl-2,3-dihydrobenzofuran-7-yl)-ethyl]-pyridine (NNC77-0020) on stimulus-secretion coupling and hormone secretion was investigated in mouse pancreatic islets and isolated alpha- and beta-cells. In the presence of elevated glucose concentrations NNC77-0020 stimulated insulin secretion concentration dependently (EC(50) 64 nM) by 200% without affecting the whole-cell K(+) current or cytoplasmic Ca(2+) levels. Capacitance measurements in single mouse beta-cells showed that intracellular application of NNC77-0020 via the recording pipette enhanced Ca(2+)-dependent exocytosis. This action was dependent on protein kinase C (PKC) and cytoplasmic phospholipase A(2) (cPLA(2)) activity and required functional granular ClC-3 Cl(-) channels. In intact islets NNC77-0020 stimulated glucose-dependent somatostatin secretion, an effect that was also dependent on PKC and cPLA(2) activity. NNC77-0020 also inhibited glucagon secretion. In single mouse alpha-cells this action was not associated with a change in spontaneous electrical activity and resulted from a reduction in the rate of Ca(2+)-dependent exocytosis. Inhibition of exocytosis by NNC77-0020 was pertussis toxin sensitive and mediated by activation of the protein phosphatase calcineurin. In conclusion, our data suggest that the imidazoline compound NNC77-0020 modulates pancreatic hormone secretion in a complex fashion, comprising glucose-dependent stimulation of insulin and somatostatin secretion and inhibition of glucagon release. These mechanisms of action constitute an ideal basis for the development of novel imidazoline-containing anti-diabetic compounds.

US$19.90

PMID: 13680090

DOI: 10.1007/s00210-003-0797-1


Other references

Alvarez, J.; Chen, W.Y., 1972: Injection of leucine into a myelinic axon: incorporation in the axoplasm and transfer to associated cells. Acta Physiologica Latino Americana 22(4): 266-269

Powers D.C., 1991: Influenza a virus specific memory cytotoxic t lymphocyte activity declines with advancing age in humans. Clinical Research 39(3): 704A

Herkenhoff K.E.; Bridges N.T.; Kirk R.L., 1999: Geologic studies of the Mars Surveyor 1998 landing area. Preliminary photoclinometric analysis of a 33 m/pixel MOC narrow-angle image of the south polar residual cap shows a root-mean-square bi-directional slope at the limit of image resolution of 1.6 degrees and a maximum slope of 6 degrees.

Christie, L.R.; Harriott, J.A.; Mitchell, S.Y.; Fletcher, H.M.; Bambury, I.G., 2009: Shoulder dystocia in a Jamaican cohort. To assess the risk factors for shoulder dystocia in Jamaica. A retrospective cohort analysis of all cases of shoulder dystocia, and birth weight-matched controls identified from January 1, 2000 to December 31, 2004. Multiple factors were analyzed...

Zaka U.Rab M., 1984: The european tadpole shrimp triops cancriformis crustacea notostraca triopsidae as a pest of rice plantations in kashmir india. Journal of Entomological Research (New Delhi) 8(1): 103-105

Rosa-Jiménez, F.; Gassó de Campos, M.; Camacho Reina, M.V.; Vázquez de Castroviejo, E.; Hernández Burruezo, J.J.; Pousibet Sanfeliú, H., 1997: Macro creatine kinase type 1 as a cause of increase of CF-MB isoenzyme. Apropos of 7 cases. The macro-creatine kinase type 1 is a complex of IgG linked to the BB fraction of the creatine kinase enzyme. Its presence in serum interferes with the immunoinhibition methods normally used in emergency room laboratories that produce false elevat...

Anonymous, 1909: Small Places Do Great Things. California State Journal of Medicine 7(1): 3-3

Luckmann, J.; Holste, U., 2005: First record of Meloe rugosus Marsham, 1802 for North-Rhine Westphalia (Coleoptera: Meloidae). The meloid beetle Meloe rugosus is recorded for the first time from North-Rhine Westphalia, Germany.

Mitchison, D.A., 1995: Rifabutin in the treatment of newly diagnosed pulmonary tuberculosis. Tubercle and Lung Disease 76(3): 277-277

Hirono M.; Igarashi M.; Matsumoto S., 1970: Short and auto feedback control of pituitary follicle stimulating hormone secretion. Neuroendocrinology 6(5-6): 274-282