Differential effects of 3 classes of antidiabetic drugs on olanzapine-induced glucose dysregulation and insulin resistance in female rats

Boyda, Heidi N.; Procyshyn, Ric M.; Tse, Lurdes; Hawkes, Erin; Jin, Chen Helen; Pang, Catherine C.Y.; Honer, William G.; Barr, Alasdair M.

doi:10.1503/jpn.110140

Cited by 51 publications

(45 citation statements)

References 67 publications

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“…Unfortunately, many commonly prescribed glucose-lowering medications are only partially effective in reducing these excursions in blood glucose (Boyda et al, 2012). In the current study we demonstrate that AICAR increases hepatic and skeletal muscle AMPK activity as demonstrated by increases in the phosphorylation of AMPK, or its downstream substrate, ACC.…”

Section: Discussionsupporting

confidence: 51%

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AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

Bush

Townsend

Wright

2018

J Pharmacol Exp Ther

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Section: Discussionsupporting

confidence: 51%

“…Given this, it is important to identify approaches to offset the acute metabolic side effects of these drugs. Unfortunately, many commonly prescribed glucose-lowering drugs (metformin, rosiglitazone, or glyburide) are not entirely effective in protecting against acute SGA-induced impairments in glucose homeostasis (Boyda et al, 2012).…”

Section: Downloaded Frommentioning

confidence: 99%

AICAR Prevents Acute Olanzapine-Induced Disturbances in Glucose Homeostasis

Bush

Townsend

Wright

2018

J Pharmacol Exp Ther

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“…A similar protocol was repeated for rosiglitazone and glyburide. Findings suggested partial reversal of glucose intolerance by both rosiglitazone and Met, but not glyburide (Boyda et al 2012). In the second study, which followed a similar protocol, Met, as well as glyburide, significantly decreased glucose levels during the IP-GTT, whereas rosiglitazone, in contrast to the earlier study, failed to do so.…”

Section: Discussionmentioning

confidence: 72%

“…These reports differ from one another with respect to AP treatment dose and duration, as well methods of assessing glucose metabolism (e.g., stand-alone measures of fasting insulin and glucose, GTTs). In general, incretins (Lykkegaard et al 2008, Smith et al 2009) and Met (Adeneye et al 2011, Boyda et al 2012, 2014 appear to improve metabolic indices, whereas the data have been more variable for sulfonylureas and thiazolidinediones (Arulmozhi et al 2006, Boyda et al 2012, 2014.…”

Section: Discussionmentioning

confidence: 99%

“…Two separate studies by Boyda examined acute Ola (7.5 mg/kg or 15 mg/kg) administration, thus avoiding the confounding effects of changes in adiposity. These studies examined the differential effects of Met (100 mg/kg or 500 mg/kg), rosiglitazone and glyburide, according to single (Boyda et al 2012) or combination treatment (Boyda et al 2014) paradigm, on glucose tolerance and insulin sensitivity (HOMA-IR). Met was given at 1100 h on day 1, and following an overnight fast, rats received (day 2) a single i.p.…”

Section: Discussionmentioning

confidence: 99%

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Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance

Remington

Teo

Wilson

et al. 2015

Journal of Endocrinology

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Antipsychotics (APs) are linked to diabetes, even without weight gain. Whether anti-diabetic drugs are efficacious in reversing the direct effects of APs on glucose pathways is largely undetermined. We tested two metformin (Met) doses to prevent impairments seen following a dose of olanzapine (Ola) (3 mg/kg); glucokinetics were measured using the hyperinsulinemic-euglycemic clamp (HIEC). Met (150 mg/kg; nZ13, or 400 mg/kg; nZ11) or vehicle (Veh) (nZ11) was administered through gavage preceding an overnight fast, followed by a second dose prior to the HIEC. Eleven additional animals were gavaged with Veh and received a Veh injection during the HIEC (Veh/Veh); all others received Ola. Basal glucose was similar across treatment groups. The Met 400 group had significantly greater glucose appearance (R a ) in the basal period (i.e., before Ola, or hyperinsulinemia) vs other groups. During hyperinsulinemia, glucose infusion rate (GINF) to maintain euglycemia (reflective of whole-body insulin sensitivity) was higher in Veh/Veh vs other groups. Met 150/Ola animals demonstrated increased GINF relative to Veh/Ola during early time points of the HIEC. Glucose utilization during hyperinsulinemia, relative to basal conditions, was significantly higher in Veh/Veh vs other groups. The change in hepatic glucose production (HGP) from basal to hyperinsulinemia demonstrated significantly greater decreases in Veh/Veh and Met 150/Ola groups vs Veh/Ola. Given the increase in basal R a with Met 400, we measured serum lactate (substrate for HGP), finding increased levels in Met 400 vs Veh and Met 150. In conclusion, Met attenuates hepatic insulin resistance observed with acute Ola administration, but fails to improve peripheral insulin resistance. Use of supra-therapeutic doses of Met may mask metabolic benefits by increasing lactate.

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