Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization

Eilers, F.; Bartels, H.; Jungermann, Kurt

doi:10.1007/bf00571874

Cited by 21 publications

(9 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Yet, enzyme activity was not aVected. This, however, is not surprising because the increase in enzyme activity follows the physiological increase in mRNA with a time lag of 6 h at least (Eilers et al 1993), a period in time, which was not investigated in the present study.…”

Section: Mechansim Of Il6 Inhibition Of Pck Gene Expressioncontrasting

confidence: 46%

“…* Values are diVerent from untreated controls at the P · 0.025 level (Student's t test for unpaired values). pv Perivenous, pp periportal expression is low, respectively (Bartels et al 1989;Eilers et al 1995Eilers et al , 1993. In the present study, IL6 inhibited the increase in PCK1 mRNA during the initial phase of fasting, from 6 a.m. to noon in the periportal zone of the liver (Fig.…”

Section: Mechansim Of Il6 Inhibition Of Pck Gene Expressionmentioning

confidence: 42%

See 1 more Smart Citation

Impact of interleukin-6 on the glucose metabolic capacity in rat liver

Lienenlüke¹,

Christ

2007

Histochem Cell Biol

View full text Add to dashboard Cite

The actute phase reaction mediated by the proinXammatory cytokine IL6 initiates a number of metabolic changes in the liver, which may contribute to the pathogenesis of the septic shock during prolonged exposition. Here, the impact of IL6 on the hepatic glucose providing capacity was studied by monitoring glycogen degradation and the expression of the gluconeogenic phosphoenolpyruvate carboxykinase (PCK1) in rat livers during the daily feeding rhythm. Eight hours after i.p. injection of IL6, mRNA levels of 2-macroglobulin, a prominent acute phase reactant in rat liver, were elevated as shown by Northern blot analysis and in situ hybridization (ISH). PCK1 mRNA levels were decreased by IL6 to 50% of levels in untreated animals due to the reduction of PCK1 mRNA in the periportal zone of the liver as shown by ISH. PCK1 enzyme activity was not aVected by IL6. Glycogen degradation was accelerated by IL6, which led to nearly complete depletion of glycogen pools in periportal areas 8 h after IL6 injection. This was very likely due to inhibition of glycogen pool replenishment. Thus, the depletion of glycogen stores in the liver might contribute to the impairment of hepatic glucose production during prolonged acute phase challenge.

show abstract

Section: Mechansim Of Il6 Inhibition Of Pck Gene Expressioncontrasting

confidence: 46%

Section: Mechansim Of Il6 Inhibition Of Pck Gene Expressionmentioning

confidence: 42%

Impact of interleukin-6 on the glucose metabolic capacity in rat liver

Lienenlüke¹,

Christ

2007

Histochem Cell Biol

View full text Add to dashboard Cite

show abstract

“…Thus, insulin resistance and diabetes are not associated with a reduction in islet GCK activity in ZF and ZDF rats. There was, however, a specific 50% reduction in GCK mRNA levels in the ZF and ZDF rats (Table 2), a result that indicates there are posttranscriptional mechanisms regulating GCK activity, as has been previously suggested (10,21,22). The nature of these mechanisms is unknown, but could include increased stability of GCK protein or higher rates of translation of GCK mRNA.…”

Section: Relationship Between Glucose Phosphorylating Activity and Bamentioning

confidence: 66%

Changes in Pancreatic Islet Glucokinase and Hexokinase Activities With Increasing Age, Obesity, and the Onset of Diabetes

et al. 1997

View full text Add to dashboard Cite

We examined changes in high- and low-Km glucose phosphorylating activity in pancreatic islet extracts from the prediabetic Zucker diabetic fatty (ZDF) rat between 5-6 weeks and 12 weeks of age (after the onset of diabetes). Comparisons were made between the activity observed in the ZDF rat and that seen in the ZDF lean control (ZLC) rat and the obese nondiabetic Zucker fatty (ZF) rat. At 5-6 weeks of age, insulin resistant ZDF and ZF rats were hyperinsulinemic, compared with the ZLC rat, but had normal plasma glucose levels. Kinetic parameters (Vmax and Km for glucose) of hexokinase (HK) and Km of glucokinase (GCK) did not differ between groups. Islet GCK activity for ZDF and ZF rats was 1.7-fold greater than in ZLC rats (P < 0.02 and P < 0.001, respectively). By 12 weeks of age, hypersecretion of insulin at 5.0 mmol/l glucose was observed in perifused islets from both obese groups relative to the ZLC rat. Islets from ZDF rats failed to increase insulin secretion in response to increased glucose concentration. Group differences in the kinetic parameters for GCK or in the Km values for HK were not significant. Islet HK activity for ZDF and ZF rats was 1.9-fold (P < 0.05) and 1.7-fold (P < 0.05) greater, respectively, than for ZLC rats. Compared with the 5- to 6-week-old animals, HK activity increased 3.1-fold (P < 0.001), 2.5-fold (P < 0.002), and 2.0-fold (P < 0.05) for ZDF, ZF, and ZLC rats, respectively. Differences in GCK activity between 5- to 6- and 12-week-old rats were not significant for any of the groups. We conclude: 1) increased islet glucose phosphorylating activity is present in insulin resistant and hyperinsulinemic ZF and ZDF rats, relative to the ZLC rat; 2) at 12 weeks of age, hyperinsulinemic ZDF and ZF rats demonstrated significant increases in HK activity, compared with lean controls; and 3) deficiency in GCK activity does not explain failure of diabetic ZDF islets to respond to glucose, since differences between diabetic ZDF and nondiabetic ZF rats were not statistically significant. Increases in pancreatic islet phosphorylating activity seem to be important in maintaining basal hyperinsulinemia in insulin-resistant animals, but do not appear to play a role in the progression to glucose intolerance and diabetes.

show abstract

“…GK and GKRP are not expressed homogenously in all the parenchymal cells in the liver. GK is expressed from periportal to perivenous areas in an increasing gradient in normal (18) and ZDF rats (data not shown). Even in perivenous areas, the intensities of immunofluorescence of GK and GKRP vary among hepatocytes (23).…”

Section: Methodsmentioning

confidence: 90%

A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes

Shin

Torres²,

Catlin³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Shin J-S, Torres TP, Catlin RL, Donahue EP, Shiota M. A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes. Am J Physiol Regul Integr Comp Physiol 292: R1381-R1390, 2007. First published January 4, 2007; doi:10.1152/ajpregu.00260.2006.-Effect of stimulation of glucokinase (GK) export from the nucleus by small amounts of sorbitol on hepatic glucose flux in response to elevated plasma glucose was examined in 6-h fasted Zucker diabetic fatty rats at 10 wk of age. Under basal conditions, plasma glucose, insulin, and glucagon were ϳ8 mM, 2,000 pmol/l, and 60 ng/l, respectively. Endogenous glucose production (EGP) was 44 Ϯ 4 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 . When plasma glucose was raised to ϳ17 mM, GK was still predominantly localized with its inhibitory protein in the nucleus. EGP was not suppressed. When sorbitol was infused at 5.6 and 16.7 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 , along with the increase in plasma glucose, GK was exported to the cytoplasm. EGP (23 Ϯ 19 and 12 Ϯ 5 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) was suppressed without a decrease in glucose 6-phosphatase flux (145 Ϯ 23 and 126 Ϯ 16 vs. 122 Ϯ 10 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 without sorbitol) but increased in glucose phosphorylation as indicated by increases in glucose recycling (122 Ϯ 17 and 114 Ϯ 19 vs. 71 Ϯ 11 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ), glucose-6-phosphate content (254 Ϯ 32 and 260 Ϯ 35 vs. 188 Ϯ 20 nmol/g liver), fractional contribution of plasma glucose to uridine 5Ј-diphosphateglucose flux (43 Ϯ 8 and 42 Ϯ 8 vs. 27 Ϯ 6%), and glycogen synthesis from plasma glucose (20 Ϯ 4 and 22 Ϯ 5 vs. 9 Ϯ 4 mol glucose/g liver). The decreased glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake may result from failure of the sugar to activate GK by stimulating the translocation of the enzyme. obese-type 2 diabetes; glucokinase regulatory protein EXCESSIVE POSTPRANDIAL HYPERGLYCEMIA is a prominent and early defect in subjects with type 2 diabetes, which is the result, at least in part, from an inadequate suppression of net hepatic glucose production (NHGP) (15,34,36) and an insufficient increase in hepatic glucose uptake (HGU) (6,7,21). Glucoseinduced suppression of NHGP was associated with increased hepatic glucose phosphorylation (47) and was abolished by inhibiting hepatic glucokinase (GK) activity in normal rats (5). This suggests that increased hepatic GK flux mediates glucose's effect not only to increase HGU, but also to decrease NHGP by the opposition of glucose 6-phosphatase flux. Basu et al. (6,7) showed that in type 2 diabetic patients, lower splanchnic glucose uptake in the face of hyperglycemic hyperinsulinemia was associated with a blunted increase in glucose phosphorylation. This implies impaired activity of GK in the liver of these patients.Studies using mouse models showed a large impact of altered hepatic GK expression in regulating postabsorptive blood glucose levels and hyperglycemia-induced HGU (35). However, decreased hepatic GK activity is not always present in patients (8,...

show abstract

Zonal expression of the glucokinase gene in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization

Cited by 21 publications

References 46 publications

Impact of interleukin-6 on the glucose metabolic capacity in rat liver

Impact of interleukin-6 on the glucose metabolic capacity in rat liver

Changes in Pancreatic Islet Glucokinase and Hexokinase Activities With Increasing Age, Obesity, and the Onset of Diabetes

A defect in glucose-induced dissociation of glucokinase from the regulatory protein in Zucker diabetic fatty rats in the early stage of diabetes

Contact Info

Product

Resources

About