Migration of Macrophage-Like Cells within Encapsulated Islets of Langerhans Maintained in Tissue Culture

1995 ◽  
Vol 4 (5) ◽  
pp. 529-534 ◽  
Author(s):  
Robert B. Fraser ◽  
Malcolm A. Macaulay ◽  
James R. Wright ◽  
Anthony M. Sun ◽  
Geoffrey Rowden

Islets of Langerhans isolated from the pancreas and encapsulated in alginate-polylysine-alginate microspheres can potentially serve as a self-regulating supply of insulin in response to glucose loads. A longitudinal ultrastructural and immunohistochemical study of encapsulated rat islets cultured in CMRL-1969 media at a constant glucose concentration of 5.5 mmol/L (100 mg%) allowed several observations. First, acinar cells, which remain attached to isolated islets, disappeared within 1 wk in tissue culture. Damaged endocrine cells also disappeared at this time. Phagocytic cells having ultrastructural features suggesting that they are macrophages emerged from the islets within about a week and ingested portions of the inner layer of capsule polymer. These macrophage-like cells retained these polymers until their death which occurred at around 1-2 mo after isolation; at no time did we observe phagocytic cells actually breaching the microsphere capsules. Beta cells remained well-granulated over 90 days of culture but accumulated lipofuscin-like residual bodies. Under these conditions, these bodies began to accumulate appreciably after about one week in culture.

1980 ◽  
Vol 239 (2) ◽  
pp. E132-E138
Author(s):  
E. G. Siegel ◽  
C. B. Wollheim ◽  
G. W. Sharp ◽  
L. Herberg ◽  
A. E. Renold

The involvement of Ca2+ in the impaired insulin release of diabetic C57BL/KsJ-db/db mice was studied. Twenty-week-old severely hyperglycemic mice were compared to nondiabetic C57BL/KsJ mice as controls. Collagenase-isolated islets were maintained for 46 h in tissue culture allowing for equilibration at the same glucose concentration (8.3) mM). The insulin content of both types of islets was similar. In control islets preloaded during culture with 45Ca2+ glucose-induced insulin release was associated with increased 45Ca2+ effux. Islets from diabetic mice showed markedly reduced insulin response to glucose and a smaller increase in 45Ca2+ efflux. Because insulin release was strikingly potentiated by 3-isobutyl-1-methylxanthine (IBMX), even more than in control islets, there was no generalized release defect. In both types of islets, IBMX potentiation was accompanied by a further enhanced 45Ca2+ efflux, possibly suggesting that cAMP effects are associated with increased cytosol Ca2+% concentrations. As Ca2+ uptake was stimulated by glucose in both types of islets, a defect may lie in the mechanism by which glucose uses cellulr calcium to raise cytosol Ca2+ in the beta-cell of these diabetic mice.


1982 ◽  
Vol 2 (11) ◽  
pp. 867-876 ◽  
Author(s):  
I. Swenne

The regulatory role of cyclic AMP (cAMP) in the growth and insulin production of the islet organ in vitro has been investigated. The effects of dibutyryl cyclic AMP (dbcAMP), theophylline, and 3-isobutyl-1-methylxanthine (IBMX) on DNA replication and on the biosynthesis of RNA and insulin in fetal rat islets of Langerhans maintained in tissue culture have been studied. Raising the glucose concentration from 2.7 mM to 16.7 mM caused a two-fold increase in DNA replication. Both dbcAMP and theophylline markedly inhibited the DNA replication at all glucose Concentrations studied. Low concentrations of IBMX stimulated DNA synthesis. However, at higher concentrations of this drug, known to considerably increase the islet cAMP levels, a marked inhibition of islet DNA replication was observed. Both (pro)insulin and total protein biosynthesis were stimulated by glucose, whereas dbcAMP stimulated only the (pro)insulin biosynthesis. Since glucose is known to raise islet intracellular levels of cAMP, which is known to be an inhibitor of cellular proliferation, the observed glucose stimulation of both islet-cell DNA replication and insulin production appeared conflicting. It is suggested that this dual effect of glucose may depend on a stimulation of proliferation in a limited pool of islet cells which may not exhibit an increase in cAMP.


Diabetologia ◽  
2000 ◽  
Vol 43 (9) ◽  
pp. 1170-1177 ◽  
Author(s):  
V. Hadjivassiliou ◽  
M. H. L. Green ◽  
I. C. Green

1977 ◽  
Vol 84 (1) ◽  
pp. 105-114 ◽  
Author(s):  
Leif Sparre Hermann ◽  
Torsten Deckert

ABSTRACT The effect of epinephrine and isoproterenol in different concentrations and adrenergic blocking agents on glucose induced insulin secretion and glucose utilization was studied in isolated islets of Langerhans from mice. Epinephrine in physiological concentrations significantly inhibited the glucose induced insulin secretion. This effect was not mediated by a change in glucose utilization but involved α-adrenergic stimulation. Isoproterenol significantly stimulated the glucose induced insulin secretion but had no effect on glucose utilization. β-adrenergic stimulation by isoproterenol at low glucose concentration was not sufficient to stimulate insulin secretion. The results are discussed in relation to current theories on the mechanism of glucose induced insulin secretion.


Diabetes ◽  
1968 ◽  
Vol 17 (4) ◽  
pp. 187-193 ◽  
Author(s):  
J. E. Vance ◽  
K. D. Buchanan ◽  
D. R. Challoner ◽  
R. H. Williams ◽  
B. Hickernell

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