Sources of endogenous glucose production in the Goto-Kakizaki diabetic rat.

Abstract:

:Plasma glucose, insulin and glucose tolerance were quantified in diabetic Goto-Kakizaki (GK) rats (342+/-45 g, n = 5) and compared with weight-matched non-diabetic Wistars (307+/-30 g, n = 8). Compared to Wistars, GK rats had higher fasting plasma insulin (219+/-50 versus 44+/-14 pmol/l, P<0.002) and glucose (9.2+/-2.3 versus 5.5+/-0.5 mmol/l, P<0.025). GK rats showed impaired glucose tolerance (IPGTT 2 h plasma glucose=14+/-1.5 versus 6.4+/-0.1 mmol/l, P<0.001). Endogenous glucose production (EGP) from glycogenolysis, phosphoenolpyruvate (PEP) and glycerol after 6 hours of fasting was quantified by a primed infusion of [U-(13)C]glucose and (2)H(2)O tracers and (2)H/(13)C NMR analysis of plasma glucose. EGP was higher in GK compared to Wistar rats (191+/-16 versus 104+/-27 mumol/kg per min, P<0.005). This was sustained by increased gluconeogenesis from PEP (85+/-12 versus 35+/-4 mumol/kg per min, P<0.02). Gluconeogenesis from glycerol was not different (20+/-3 in Wistar versus 30+/-6 mumol/kg per min for GK), and glycogenolysis fluxes were also not significantly different (76+/-23 mumol/kg per min for GK versus 52+/-19 mumol/kg per min for Wistar). The Cori cycle accounted for most of PEP gluconeogenesis in both Wistar and GK rats (85+/-15% and 77+/-10%, respectively). Therefore, increased gluconeogenesis in GK rats is largely sustained by increased Cori cycling while the maintenance of glycogenolysis indicates a failure in hepatic autoregulation of EGP.

journal_name

Diabetes Metab

journal_title

Diabetes & metabolism

authors

Sena CM,Barosa C,Nunes E,Seiça R,Jones JG

doi

10.1016/j.diabet.2007.03.002

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

296-302

issue

4

eissn

1262-3636

issn

1878-1780

pii

S1262-3636(07)00104-8

journal_volume

33

pub_type

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