Insulin, Glucagon, and Somatostatin Secretion in the Regulation of Metabolism

Unger, Roger H; Dobbs, R. E.; Orci, Lelio

doi:10.1146/annurev.ph.40.030178.001515

Cited by 201 publications

(96 citation statements)

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“…After removal of the bottom of the dish by immersion in liquid nitrogen, the identification mark surrounding the injected cluster was localized on the embedded cover glass under a phase-contrast microscope . A small block of Epon supporting the microinjected cluster was then cut from the sample, immersed for 5 min in warm (85°C) water and, subsequently, rapidly 22 Presence of intercellular communication transferred to liquid nitrogen. This procedure usually resulted in a clean separation of the cover glass from the polymerized plastic without damage to the cells.…”

Section: Electron Microscopymentioning

confidence: 99%

See 1 more Smart Citation

Direct communication of homologous and heterologous endocrine islet cells in culture.

Meda¹,

Kohen²,

Kohen³

et al. 1982

The Journal of Cell Biology

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The transfer of 6-carboxyfluorescein between islet cells in monolayer culture was observed by fluorescence microscopy, and the endocrine cells involved in this transfer were identified by immunohistochemistry and electron microscopy. The results show that carboxyfluorescein was directly exchanged between homologous B-cells and also between B-and A-or D-cells . Successive microinjections of the probe into different cells of the same cluster showed the existence of separate territories, each formed by 2-8 communicating cells. Intercellular communication was not observed after every dye microinjection, and communicating and noncom municating islet cells were found to coexist within the same cluster . The data indicate that the exchange of exogenous cytoplasmic molecules occurs between different types of endocrine islet cells. However, within a single cluster, all islet cells are not metabolically coupled to one another, at a given time.Ionic and metabolic cell-to-cell coupling (1) have been recently demonstrated between B-cells of the islets of Langerhans (2,5,8,11). In view of the heterogeneous endocrine cell composition of the islet (14) and of the possible functional interactions between various islet cells (for review, see reference 22), it was important to assess whether coupling occurred between different islet cell types .In the present study we have identified by immunohistochemistry and electron microscopy the islet cells involved in the direct exchange of 6-carboxyfluorescein, an exogenous fluorescent probe (376 mol wt) to which the cell membrane is impermeable (20). Our observations show that, in monolayer culture of neonatal endocrine pancreas, B-cells directly communicate not only with other B-cells but also with neighboring A-and D-cells, indicating that both homologous and heterologous coupling occur between differentiated islet cells . The metabolically coupled cells were found to form separate territories and to coexist with uncoupled cells within the same cluster . MATERIALS AND METHODS Islet Cell CulturesMonolayer cultures of islet cells were prepared by a modification of a collagenase-trypsin method (6) as described (18) . Briefly, the pancreases of newborn Wistar rats were enzymatically dissociated by ten successive 10-min incubations at 37°C in a Ca"-and Mg"-free phosphate-buffered saline (PBS) containing 5.6 mM glucose, 5 mg/ml trypsin (1 :250, Difco Laboratories, Detroit, Mich.) and 0.2 mg/ml of collagenase (CLS IV, Worthington Biochemical Corp., Freehold, N. J.) . The dissociated cells, collected by decantation at the end of THE JOURNAL OF CELL BIOLOGY " VOLUME 92 JANUARY 1982 221-226 © The Rockefeller University Press -0021-9525/82/01/0221/06 $1 .00 RAPID COMMUNICATIONS each of the last eight incubations, were pooled, rinsed twice by centrifugation in medium 199 (Gibco Laboratories, Grand Island Biological Co ., Grand Island, N. Y.) supplemented with 10% heat-inactivated fetal calf serum and 16 .7 mM glucose, resuspended in this medium, and plated at a concentration of 7.5 x 105 ce...

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Section: Electron Microscopymentioning

confidence: 99%

“…In view of the heterogeneous endocrine cell composition of the islet (14) and of the possible functional interactions between various islet cells (for review, see reference 22), it was important to assess whether coupling occurred between different islet cell types .…”

mentioning

confidence: 99%

Direct communication of homologous and heterologous endocrine islet cells in culture.

Meda¹,

Kohen²,

Kohen³

et al. 1982

The Journal of Cell Biology

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“…Glucagon is a 29-amino acid peptide secreted by the a cells of the pancreatic islets in response to reduced blood glucose levels (Unger et al 1978). This hormone travels via the portal blood to the liver where it activates the glucagon receptor.…”

Section: Introductionmentioning

confidence: 99%

Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes

Claus

Pan

Buxton

et al. 2007

Journal of Endocrinology

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Type 2 diabetes is characterized by reduced insulin secretion from the pancreas and overproduction of glucose by the liver. Glucagon-like peptide-1 (GLP-1) promotes glucose-dependent insulin secretion from the pancreas, while glucagon promotes glucose output from the liver. Taking advantage of the homology between GLP-1 and glucagon, a GLP-1/glucagon hybrid peptide, dual-acting peptide for diabetes (DAPD), was identified with combined GLP-1 receptor agonist and glucagon receptor antagonist activity. To overcome its short plasma half-life DAPD was PEGylated, resulting in dramatically prolonged activity in vivo. PEGylated DAPD (PEG-DAPD) increases insulin and decreases glucose in a glucose tolerance test, evidence of GLP-1 receptor agonism. It also reduces blood glucose following a glucagon challenge and elevates fasting glucagon levels in mice, evidence of glucagon receptor antagonism. The PEG-DAPD effects on glucose tolerance are also observed in the presence of the GLP-1 antagonist peptide, exendin(9-39). An antidiabetic effect of PEG-DAPD is observed in db/db mice. Furthermore, PEGylation of DAPD eliminates the inhibition of gastrointestinal motility observed with GLP-1 and its analogues. Thus, PEG-DAPD has the potential to be developed as a novel dual-acting peptide to treat type 2 diabetes, with prolonged in vivo activity, and without the GI side-effects.

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“…Whether or not its physiological actions are entirely local is an open question [2] but it has been demonstrated by radioimmunoassay that biologically active concentrations [3 ] are present in normal human plasma after a meal [4]. Somatostatin is known to be converted rapidly to a closely related product, [desAla']-somatostatin, in rat plasma in vitro and in vivo [5].…”

Section: Introductionmentioning

confidence: 99%