Background: Recent studies have suggested that hyperglycaemia influences the bile acid profile and concentrations of secondary bile acids in the gut. Introduction: This study aimed to measure changes in the bile acid profile in gut, tissues, and faeces in Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D). Method: T1D and T2D were established in a mouse model. Twenty-one seven-weeks old balb/c mice were randomly divided into three equal groups, healthy, T1D and T2D. Blood, tissue, urine and faeces samples were collected for bile acid measurements. Results: Compared with healthy mice, T1D and T2D mice showed lower levels of the primary bile acid chenodeoxycholic acid in the plasma, intestine, and brain, and higher levels of the secondary bile acid lithocholic acid in the plasma and pancreas. Levels of the bile acid ursodeoxycholic acid were undetected in healthy mice but were elevated in T1D and T2D mice. Conclusion: Bile acid profiles in other organs were variably influenced by T1D and T2D development, which suggests similarity in effects of T1D and T2D on the bile acid profile, but these effects were not always consistent among all organs, possibly since feedback mechanisms controlling enterohepatic recirculation and bile acid profiles and biotransformation are different in T1D and T2D.

Introduction: The ratio of secondary to primary bile acids changes during Type 1 Diabetes (T1D) development and these effects might be ameliorated by using cholesterol lowering drugs or hydrophilic bile acids. Probucol is a cholesterol-lowering drug, while ursodeoxycholic acid is a hydrophilic bile acid. This study investigated whether nanoencapsulated probucol with ursodeoxycholic acid altered bile acid ratios and the development of diabetes. Methods: Balb/c mice were divided into three groups and gavaged daily with either free probucol, nanoencapsulated probucol or nanoencapsulated probucol with ursodeoxycholic acid for seven days. Alloxan was injected and once T1D was confirmed the mice continued to receive daily gavages until euthanasia. Blood, tissues, faeces and urine were collected for analysis of insulin and bile acids. Results and Conclusions: Nanoencapsulated probucol-ursodeoxycholic acid resulted in significant levels of insulin in the blood, lower levels of secondary bile acids in liver and lower levels of primary bile acids in brain, while ratio of secondary to primary bile acids remains similar among all groups, except in the faeces. Findings suggests that nanoencapsulated probucol-ursodeoxycholic acid may exert a protective effect on pancreatic b-cells and reserve systemic insulin load via modulation of bile acid concentrations in the liver and brain.

Aim: Examine bile acids effects in Type 2 diabetes. Background: In recent studies, the bile acid ursodeoxycholic acid (UDCA) has shown potent anti-inflammatory effects in obese patients while in type 2 diabetics (T2D) levels of the pro-inflammatory bile acid lithocholic acid were increased, and levels of the anti-inflammatory bile acid chenodeoxycholic acid were decreased, in plasma. Objective: Hence, this study aimed to examine applications of novel UDCA nanoparticles in diabetes. Methods: Diabetic balb/c adult mice were divided into three equal groups and gavaged daily with either empty microcapsules, free UDCA, or microencapsulated UDCA over two weeks. Their blood, tissues, urine, and faeces were collected for blood glucose, inflammation, and bile acid analyses. UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Results: UDCA resulted in modulatory effects on bile acids profile without antidiabetic effects suggesting that bile acid modulation was not directly linked to diabetes treatment. Conclusion: Bile acids modulated the bile profile without affecting blood glucose levels.

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Smart polymers such as Eudragit (ED) have shown potential applications in oral drug delivery and targeted release. Probucol (PB) is a lipophilic drug used for hypercholesterolemia and possesses desirable antidiabetic effects such as antioxidant and cell protective effects. PB is highly hydrophobic and has poor bioavailability with significant inter-and intra-patient absorption, limiting its clinical applications in diabetes. This study aimed to design and analyse new PB-ED formulations with or without the absorption-enhancer chenodeoxycholic acid (CDCA). Sodium alginate-based microcapsules containing three different ED polymers (NM30D, RL30D and RS30D) were investigated with or without CDCA via scanning electron microscopy, energy dispersive X-ray spectroscopy (EDXR), confocal microscopy, osmotic stability, mechanical properties, buoyancy, release profiles (pH: 7.4), thermal stability and antioxidant effects. The effects of microcapsules on pancreatic b-cell survival, function, inflammatory profile and PB cellular uptake were analysed. All microcapsules showed uniform morphology and surface topography with CDCA being distributed evenly throughout the microcapsules. Osmotic stability was significantly improved in PB-NM30D and PB-RL30D microcapsules (p < .01 and p < .05, respectively), and PB-NM30D microcapsules displayed low buoyancy (p < .01). CDCA improved PB-NM30D effects on pancreatic b-cell function and bioenergetics, which suggests potential application of PB-NM30D-CDCA in PB delivery and diabetes treatment.