In pancreatic islets from hereditarily diabetic GK rats, [1,12 -14C] dodecanedioic acid (5.0 mM) was oxidized at a rate representing about 5 % of that of D-[U - 14C] glucose (8.3 mM). Dioic acid and hexose failed to exert any significant reciprocal effects on their respective oxidation. The production of 14CO2 from [1,12 -14C] dodecanedioic acid was proportional to its concentration in the 0.2 - 5.0 mM range. These results were essentially comparable to those obtained in islets from control rats. They extend, therefore, to GK rats the knowledge that dodecanedioic acid acts as a nutrient in pancreatic islet cells.
Key words:
[1,12 -14C] Dodecanedioic Acid - Pancreatic Islets - GK Rats
References
-
1
Greco A V, Mingrone G.
Dicarboxylic acids, an alternate fuel substrate in parenteral nutrition: an update.
Clinical Nutrition.
1995;
14
143-148
-
2
Leighton F, Bergseth S, Rortveit T, Christiansen E N, Bremer J.
Free acetate production by rat hepatocytes during peroxisomal fatty acid and dicarboxylic acid oxidation.
J Biol Chem.
1989;
264
10 346-10 350
-
3
Mortersen P B, Kølvraa S, Gregersen N.
Cyanide insensitive and clofibrate enhanced β-oxidation of dodecanedioic acid: evidence of peroxisomal β-oxidation of dicarboxylic acids.
Biochim Biophys Acta.
1982;
713
393-397
-
4
Pettersen J E.
Metabolism of hexadecanedioic acid and its mono-L-carnitine ester.
Biochim Biophys Acta.
1973;
306
1-19
-
5
Vamecq J, Draye J P.
Peroxisomal and mitochondrial β-oxidation of monocarboxylyl-CoA, ω-hydroxymonocarboxylyl-CoA and dicarboxylyl-CoA esters in tissues from untreated and clofibrate-treated rats.
J Biochem.
1989;
106
216-222
-
6
Kou Y, Tserng Shiow-Jen J.
Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates.
J Biol Chem.
1991;
266
2924-2929
-
7
Saint-Macary M, Foucher B.
Comparative partial purification of the active dicarboxylate transport system of rat liver, kidney and heart mitochondria.
Biochem Biophys Res Commun.
1985;
133
498-504
-
8
Boelsterli U A, Zimmerli B, Meier P J.
Identification and characterization of a basolateral dicarboxylate/cholate antiport system in rat hepatocytes.
Am J Physiol.
1995;
268
G797-G805
-
9
Sheridan E, Rumrich G, Ullrich K J.
Reabsorption of dicarboxylic acids from the proximal convolution of rat kidney.
Pfluegers Arch.
1983;
399
18-28
-
10
Ullrich K J, Fasold H, Rumrich G, Kloss S.
Secretion and contraluminal uptake of dicarboxylic acids in the proximal convolution of rat kidney.
Pfluegers Arch.
1984;
400
241-249
-
11
Bertuzzi A, Mingrone G, Gandolfi A, Greco A V, Salinari S.
Disposition of dodecanedioic acid in humans.
J Pharmacol Exper Ther.
2000;
292
846-852
-
12
Raguso C A, Mingrone G, Greco A V, Tataranni P A, DeGaetano A, Castagneto M.
Dicarboxylic acids and glucose utilization in humans: effect of sebacate.
JPEN.
1994;
18
9-13
-
13
Greco A V, Mingrone G, Capristo E, Benedetti G, DeGaetano A, Gasbarrini G.
The metabolic effect of dodecanedioic acid infusion in non-insulin-dependent diabetic patients.
Nutrition.
1998;
14
351-357
-
14
Beck-Nielsen H.
Insulin resistance in skeletal muscles of patients in diabetes mellitus.
Diabetes Metab Rev.
1989;
5
487-493
-
15
Falholt K, Jensens I, Lindkaer Jensen S, Mortensen H, Volund A, Heding L G, Noerskov Petersen P, Falholt W.
Carbohydrate and lipid metabolism of skeletal muscle in type 2 diabetes patients.
Diabet Med.
1988;
5
27-31
-
16
Malaisse W J, Greco A V, Mingrone G.
Effects of aliphatic dioic acids and glycerol-1,2,3-tris(dodecanedioate) on D-glucose-stimulated insulin release in rat pancreatic islets.
Br J Nutr .
2000;
84
733-736
-
17
Malaisse W J, Greco A V, Mingrone G.
Oxidation of [1,12 -14C] dodecanedioic acid by rat pancreatic islets.
Int J Mol Med.
2000;
6
453-454
-
18
Goto Y, Kakizaki M, Masaki N.
Spontaneous diabetes produced by selective breeding of normal Wistar rats.
Proc Jpn Acad.
1975;
51
80-85
-
19
Malaisse W J, Sener A.
Hexose metabolism in pancreatic islets. Feedback control of D-glucose oxidation by functional events.
Biochim Biophys Acta.
1988;
971
246-254
-
20
Bjorklund A, Yaney G, McGarry J D, Weir G.
Fatty acids and β-cell function.
Diabetologia.
1997;
40 (Suppl 3)
B21-B26
-
21
Lee Y, Hirose H, Ohneda M, Johnson J H, McGarry J D, Unger R H.
β-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte β-cell relationships.
Proc Natl Acad Sci USA.
1994;
91
10878-10 882
-
22
Milburn J L, Hirose H, Lee Y H, Nagasawa Y, Ogawa A, Ohneda M, BeltrandelRio H, Newgard C B, Johnson J H, Unger R H.
Pancreatic β-cells in obesity. Evidence for induction of functional, morphologic, and metabolic abnormalities by increased long chain fatty acids.
J Biol Chem.
1995;
270
1295-1299
-
23
Prentki M, Corkey B E.
Are the β-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?.
Diabetes.
1996;
45
273-283
-
24
Unger R.
Lipotoxicity in the pathogenesis of obesity-dependent NIDDM.
Diabetes.
1995;
44
863-870
-
25
Chen S, Ogawa A, Ohneda M, Unger R H, Foster D W, McGarry J D.
More direct evidence for a malonyl-CoA-carnitine palmitoyltransferase I interaction as a key event in pancreatic β-cell signaling.
Diabetes.
1994;
43
878-883
-
26
Warnotte C, Gilon P, Nenquin M, Henquin J C.
Mechanisms of the stimulation of insulin release by saturated fatty acids.
Diabetes.
1994;
43
703-711
-
27
Crespin S R, Greenough W B, Steinberg D.
Stimulation of insulin secretion by long-chain free fatty acids.
J Clin Invest.
1973;
53
1979-1984
-
28
Hennes M MI, Dua A, Kissebah A H.
Effect of free fatty acids and glucose on splanchnic insulin dynamics.
Diabetes.
1997;
46
57-62
-
29
Stein D T, Esser V, Stevenson B E, Lane K E, Whiteside J H, Daniels M B, Chen S, McGarry J D.
Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat.
J Clin Invest.
1996;
97
2728-2735
-
30
Elks M L.
Chronic perifusion of rat islets with palmitate suppresses glucose-stimulated insulin release.
Endocrinology.
1993;
133
208-214
-
31
Zhou Y P, Grill V E.
Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle.
J Clin Invest.
1994;
93
870-876
-
32
Zhou Y P, Grill V.
Long-term exposure to fatty acids and ketones inhibits β-cell function in human pancreatic islets of Langerhans.
J Clin Endocrinol Metab.
1995;
80
1575-1580
-
33
Zhou Y, Berggren P, Grill V.
A fatty acid-induced decrease in pyruvate dehydrogenase activity is an important determinant of β-cell dysfunction in the obese diabetic db/db mouse.
Diabetes.
1996;
45
580-586
-
34
Sako Y, Grill V.
A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and β-cell oxidation through a process likely coupled to fatty acid oxidation.
Endocrinology.
1990;
127
1580-1589
-
35
Shimabukuro M, Zhou Y T, Levi M, Unger R H.
Fatty acid-induced β-cell apoptosis: A link between obesity and diabetes.
Proc Natl Acad Sci USA.
1998;
95
2498-2502
-
36
Mingrone G ., De Gaetano A, Greco A V, Capristo E, Benedetti G, Tacchino R M, Castagneto M, Gasbarrini G.
Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids.
Diabetologia.
1997;
40
599-605
-
37
Mingrone G, Henriksen F L, Greco A V, Krogh L N, Capristo E, Benedetti E, Gastaldelli A, Castagneto M, Ferrannini E, Gasbarrini G, Beck-Nielsen H.
Triglyceride-induced diabetes associated with familial lipoprotein lipase deficiency.
Diabetes.
1999;
48
1258-1263
-
38
Mingrone G, De Gaetano A, Greco A V, Capristo E, Benedetti G, Castagneto M, Gasbarrini G.
Dodecanedioic acid infusion induces a sparing effect on whole-body glucose uptake, mainly in non-insulin-dependent diabetes mellitus.
Br J Nutr.
1997;
78
723-735
W. J. Malaisse, M.D., Ph.D.
Laboratory of Experimental Medicine
Brussels Free University
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