Effect of INGAP-PP upon islet glucokinase activity and glucose metabolism.

MAIZTEGUI B; BORELLI MI; GAGLIARDINO JJ

Natal, Rio Grande do Norte

Congreso; The Annual Meeting of EASD Islet Study Group (ISG 2011); 2011

EASD (European Association for the Study of Diabetes) Islet Study Group

Background and Aims: INGAP-PP enhances insulin secretion and increases B-cell mass; however, its possible effect upon islet metabolism is still unknown. Thus, we have studied the effect of INGAP-PP upon insulin secretion, glucose (G) metabolism and glucokinase (GK) activity in cultured islets isolated from normal rats. Methods: Islets were isolated from pancreases of normal adult male Wistar rats by collagenase digestion and cultured for 4 days in RPMI 1640 pH 7.4, containing 2 g/L NaHCO3, 5% (v/v) fetal calf serum, 1% penicillin/streptomycin and 10 mM glucose in a humid atmosphere (5% CO2/95% O2), with or without the addition of 10 µg/ml INGAP-PP. The islets were thereafter rinsed in KRB and preincubated in 1.0 ml of KRB containing 1.5% (w/v) BSA and 3.3 mM glucose at 37 °C for 45 min. After this period, groups of islets were incubated with glucose 3.3, 8.3 or 16.7 mM glucose to study insulin release, glucose metabolism (14CO2 and 3H2O production from labeled glucose) and GK activity (bioassay). Results: C vs. INGAP-PP (* p<0.05): Insulin secretion (ng/islet/h): 3.3 mM G:  0.26 ± 0.03 vs. 0.34 ± 0.07; 8.3 mM G: 1.59 ± 0.19 vs. 2.63 ± 0.32*; 16.7 mM G:  2.89 ± 0.26 vs. 4.66 ± 0.45*. Glucose oxidation: 14CO2 (pmol/ islet/ 120 min):  3.3 mM G: 0.34 ± 0.04 vs. 0.48 ± 0.07; 8.3 mM G: 0.37 ± 0.06 vs. 0.74 ± 0.12*; 16.7 mM G: 0.63 ± 0.10 vs. 1.43 ± 0.14*; Glucose utilization 3H2O (pmol/ islet/ 120 min): 3.3 mM G: 1.30 ± 0.22 vs. 1.78 ± 0.32; 8.3 mM G: 1.98 ± 0.25 vs. 3.15 ± 0.40*; 16.7 mM G: 3.28 ± 0.40 vs. 5.78 ± 0.65*. GK activity (pmol/islet/h): 2.44 ± 0.65 vs. 4.77 ± 0.27*. Conclusions: the positive modulatory effect of INGAP-PP upon GK activity and glucose metabolism can partly explain its enhancing effect upon glucose-induced insulin secretion; it is not clear as yet the mechanism by which INGAP-PP increased GK activity. These data suggest that INGAP-PP may become a potential treatment candidate in cases of impaired islet glucose metabolism/insulin secretion.