Effects of insulin and‐like growth factor (IGF‐I)on oligodendrocyte‐enriched glial culture

Abstract

The brains from 1-week-old rat pups were used to prepare cultures of glial cells. After 24 hr in culture the cells were changed to a chemically defined serum-free medium (CDM). We have used antibodies against gangliosides (monoclonals A2B5 and LB1) and against galactocerebrosides to monitor the influence of insulin on the development of oligodendrocytes from precursor cells. In these oligodendrocyte-enriched cultures we investigated the influence of insulin and IGF-I on the activity of the marker enzymes 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) and glycerol-3-phosphate dehydrogenase (G3PDH), and on lipid metabolism. 1) Incorporation of [35S] sulfate into sulfolipids was stimulated by insulin (optimal concentration 100 nM). A sharp peak in sulfolipid synthesis was seen at day 5-6 in culture. 2) Insulin stimulated the expression of CNPase and G3PDH in culture. 3) The stimulating effect of insulin on sulfolipid synthesis, CNPase, and G3PDH activity was mimicked by IGF-I (13 nM). 4) The incorporation of [35S] into sulfolipids and [2-3H]acetate into fatty acids and cholesterol was reversibly reduced by temporary omission of insulin from the medium. These results indicate that insulin and IGF-I stimulate the development of oligodendrocytes in our culture system and that insulin has a general anabolic effect on the lipid metabolism of the cells.

Regulation of cerebroside sulfotransferase activity in cultured oligodendrocytes: Effect of growth factors and insulin

“…This time is equivalent to 14 days postnatal, and our results for CST maximal activity (12 DIV) are thus in accordance with these previous observations. Our results are also in accordance with those of van der Pal et al (1988) who observed a maximal 35S incorporation into sulfatides at a time equivalent to 12 days postnatal in OL enriched glial cultures.…”

Insulin-like growth factor I gene expression is induced in astrocytes during experimental demyelination.

“…The fact that the time course of IGF-I receptor immunostaining in oligodendroglia parallels the return of myelinrelated proteins as shown by levels of transcripts in the present study, by the presence of myelin proteins in oligodendroglia (33), and by myelin regeneration in electron micrographs (21,22,34) suggests that IGF action in this setting may stimulate functions of differentiated oligodendroglia, as demonstrated in vitro (7)(8)(9)(10)20). Thus, we conclude from the present findings that oligodendroglial injury and/or myelin breakdown trigger astroglial IGF-I production and that IGF-I released from astrocytes may diffuse in a paracrine mode to act on IGF-I receptors on nearby oligodendroglia and stimulate oligodendroglial functions that produce myelin regeneration.…”

“…It promotes the mitosis of sympathetic neuroblasts, the survival of fetal neurons, and the stimulation of neurite outgrowth in motor and sensory neurons, and it induces oligodendrocyte differentiation and myelin synthesis (3)(4)(5)(6)(7)(8)(9)(10). These effects are mediated by the type I IGF receptor, which is a membranebound tyrosine kinase with significant homology to the insulin receptor (11,12).…”

“…Evidence that IGF-I has a role in myelination is the finding that transgenic mice overexpressing IGF-I (19) have increased brain myelin content (20). Also, several studies have shown that IGFs have potent and highly specific effects on oligodendrocytes in vitro (7)(8)(9)(10). However, except for the olfactory system, very little IGF-I is normally detected in the mature rodent brain (16)(17)(18).…”

Insulin Promotes the Hydrolysis of a Glycosyl Phosphatidylinositol in Cultured Rat Astroglial Cells

“…In this sense, insulin is known to modify the metabolic activities of astroglial cells through the stimulation of glucose uptake and protein and lipid synthesis (Kum et al, 1987(Kum et al, , 1988Van der Pal et al, 1988). Because TOF-I does not produce OPT hydrolysis in astrocytes, other mechanisms of action may be related to the effects of this polypeptide, i.e., mitogenesis of astrocytes and promotion of glial cell development (Ballotti et al, 1987;Van der Pal et al, 1988). It is interesting that TGF-I receptors, IRS-1, and P1-3' kinase have been identified in rat brain and are components of another signal transduction pathway involved in the mechanism of both TGF-I and insulin action (Folli et al, 1994).…”