Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2018 Jun;8(3):543-551.
doi: 10.1007/s13346-017-0473-5.

The biological effects of the hypolipidaemic drug probucol microcapsules fed daily for 4 weeks, to an insulin-resistant mouse model: potential hypoglycaemic and anti-inflammatory effects

Armin Mooranian  1 , Rebecca Negrulj  1 , Ryu Takechi  2 , John Mamo  2 , Hesham Al-Sallami  3 , Hani Al-Salami  4
Affiliations

The biological effects of the hypolipidaemic drug probucol microcapsules fed daily for 4 weeks, to an insulin-resistant mouse model: potential hypoglycaemic and anti-inflammatory effects

Armin Mooranian et al. Drug Deliv Transl Res. 2018 Jun.

Abstract

Probucol (PB) is an hypolipidaemic drug with potential antidiabetic effects. We showed recently using in vitro studies that when PB was incorporated with stabilising lipophilic bile acids and microencapsulated using the polymer sodium alginate, the microcapsules showed good stability but poor and irregular PB release. This suggests that PB microcapsules may exhibit better release profile and hence better absorption, if more hydrophilic bile acids were used, such as ursodeoxycholic acid (UDCA). Accordingly, this study aimed to produce PB-UDCA microcapsules and examine PB absorption and antidiabetic effects in our mouse-model of insulin-resistance and diabetes (fed high-fat diet; HFD). The study also aimed to examine the effects of the microcapsules on the bile acid profile. Healthy mice (fed low-fat diet; LFD) were used as control. Seventy mice were randomly allocated into seven equal groups: LFD, HFD given empty microcapsules, HFD given metformin (M), HFD given standard-dose probucol (PB-SD), HFD given high-dose probucol (PB-H), HFD given UDCA microcapsules and HFD given PB-UDCA microcapsules. Blood glucose (BG), inflammatory biomarkers (TNF-α, IFN-γ, IL-1β, IL-6, IL-10, IL-12 and IL-17), plasma cholesterol, non-esterified fatty acids and triglycerides were analysed together with plasma bile acid and probucol concentrations. PB-UDCA microcapsules reduced BG in HFD mice, but did not reduce inflammation or improve lipid profile, compared with positive control (HFD) group. Although PB-UDCA microcapsules did not exert hypolipidaemic or antiinflammatory effects, they resulted in significant hypoglycaemic effects in a mouse model of insulin resistance, which suggests potential applications in insulin-resistance and glucose haemostasis.

Keywords: Animal studies; Bile acid; Cholesterol; Diabetes; Inflammation; Microencapsulation; Probucol.

PubMed Disclaimer

References

    1. Hordern MD, Dunstan DW, Prins JB, Baker MK, Singh MA, Coombes JS. Exercise prescription for patients with type 2 diabetes and pre-diabetes: a position statement from Exercise and Sport Science Australia. J Sci Med Sport. 2012;15(1):25–31. https://doi.org/10.1016/j.jsams.2011.04.005 . - DOI - PubMed
    1. Kwak JH, Paik JK, Kim HI, Kim OY, Shin DY, Kim HJ, et al. Dietary treatment with rice containing resistant starch improves markers of endothelial function with reduction of postprandial blood glucose and oxidative stress in patients with prediabetes or newly diagnosed type 2 diabetes. Atherosclerosis. 2012;224(2):457–64. https://doi.org/10.1016/j.atherosclerosis.2012.08.003 . - DOI - PubMed
    1. Icks A, Claessen H, Strassburger K, Tepel M, Waldeyer R, Chernyak N, et al. Drug costs in prediabetes and undetected diabetes compared with diagnosed diabetes and normal glucose tolerance: results from the population-based KORA Survey in Germany. Diabetes Care. 2013;36(4):e53–4. https://doi.org/10.2337/dc12-0997 . - DOI - PubMed - PMC
    1. Rhee SY, Chon S, Oh S, Kim SW, Kim JW, Kim YS, et al. Insulin secretion and insulin resistance in newly diagnosed, drug naive prediabetes and type 2 diabetes patients with/without metabolic syndrome. Diabetes Res Clin Pract. 2007;76(3):397–403. https://doi.org/10.1016/j.diabres.2006.09.035 . - DOI - PubMed
    1. Duksal T, Tiftikcioglu BI, Bilgin S, Kose S, Zorlu Y. Role of inflammation in sensory neuropathy in prediabetes or diabetes. Acta Neurol Scand. 2016;133(5):384–90. https://doi.org/10.1111/ane.12474 . - DOI - PubMed

Publication types

MeSH terms

LinkOut - more resources