J. Rasschaert et al., PANCREATIC-ISLET RESPONSE TO DICARBOXYLIC-ACID ESTERS IN RATS WITH TYPE-2 DIABETES - ENZYMATIC, METABOLIC AND SECRETORY ASPECTS, Journal of molecular endocrinology, 13(2), 1994, pp. 209-217
This study aimed to compare the metabolic and secretory responses of p
ancreatic islets from animals with non-insulin-dependent diabetes to D
-glucose with the effects of the methyl esters of succinic acid (SME)
and glutamic acid (GME). The insulin secretory response to D-glucose w
as impaired in islets from rats with diabetes which was either inherit
ed (Goto-Kakizaki (GK) rats) or acquired (streptozotocin-treated (STZ)
rats). This coincided with a preferential alteration of oxidative rel
ative to total glycolysis in intact islets and a selective defect of F
AD-linked mitochondrial glycerophosphate dehydrogenase (m-GDH) in isle
t homogenates. This enzymatic defect was also found in purified B cell
s from STZ rats. It contrasted both with unaltered activities of gluta
mate dehydrogenase and succinate dehydrogenase in the islets of diabet
ic animals and with a normal or even increased activity of m-GDH in th
e livers of GK and STZ rats. The oxidation of [1,4-C-14]SME and [U-C-1
4]GME appeared decreased in islets of GK or STZ animals when compared
with control rats, but no significant difference between control and d
iabetic rats was observed when the oxidative data were expressed relat
ive to the rate of [U-C-14]GME hydrolysis. Nevertheless, the absolute
values for insulin release evoked by a non-metabolized analogue of L-l
eucine (BCH), by SME and by the association of BCH with either SME or
GME were invariably lower in islets of GK and STZ rats than in those o
f control animals. These findings indicate that the enzymatic and meta
bolic situation in islets of GK and STZ rats could allow the expressio
n of the insulinotropic potential of SME and GME, even if their immedi
ate secretory effects are impaired in the islets of these diabetic ani
mals.