Chronic intake of 4-Methylimidazole induces Hyperinsulinemia and Hypoglycaemia via Pancreatic Beta Cell Hyperplasia and Glucose Dyshomeostasis

Abstract

Caramel colours are the preferential food colouring agent globally, reaches wide age groups through eatables. Colas, a sweetened carbonated drink are most common caramel coloured beverage and its consumption is linked with diabetes, obesity, pancreatic cancer and other endocrine disorders. A major by-product produced during caramelization is 4-methylimidazole (4-MEI) that is detected in noteworthy concentrations in colas and other beverages. Previous studies revealed the neurotoxic and carcinogenic potential of 4-MEI in animals at higher doses but the effect of 4-MEI at theoretical maximum daily intake dose on glucose homeostasis is unexplored. Here, mice treated with 4-MEI (32 µg/kg bodyweight/day) for seven weeks exhibited severe hypoglycaemia and hyperinsulinemia mediated by hyperplasia of pancreatic beta cells and induces metabolic alterations. On combinatorial treatment, 4-MEI suppressed the glucogenic potential of non-artificial sweeteners and promotes lipogenesis. Furthermore, increased levels of C-peptide, LDL-cholesterol and triglycerides were observed in the humans with regular intake of 4-MEI containing beverages. In summary, 4-MEI induced pancreatic beta cell hyperplasia and leads to disruption of glucose and lipid homeostasis. This study suggests the need for further assessment and reconsideration of the wide usage of 4-MEI containing caramels as food additives.

O subproduto do corante caramelo IV em alimentos pode causar toxicidade?

“…De acordo com os resultados encontrados neste estudo, o metabolismo do 4-MEI pareceu semelhante nos modelos experimentais rato e camundongo. Rekha et al (2018) avaliaram o efeito do 4-MEI no metabolismo da glicose de camundongos que foram tratados com 0,032 mg/Kg de peso corporal de 4-MEI por via oral, usando uma sonda por sete semanas continuamente. Todos os animais expostos a 4-MEI exibiram uma diminuição constante no nível de glicose no sangue, atingindo a condição hipoglicêmica após Research, Society and Development, v. 10, n. 8, e48210817537, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i8.17537 6 35 dias (p<0,0001), que prolongou-se até o final do experimento.…”

Anti‐Obesity Effect of T. Chebula Fruit Extract on High Fat Diet Induced Obese Mice: A Possible Alternative Therapy

“…After the oral administration of glucose (3 g kg −1 body weight), the blood glucose at an interval of 30 min till 120 min was measured from the blood collected from tail puncture. [43] Biochemical Analysis: Serum samples obtained from the mice were used for biochemical analysis. The total cholesterol and triglyceride levels in serum were determined as per the protocol recommended by Sigma-Aldrich (MAK043 and TR0100).…”

“…After the oral administration of glucose (3 g kg −1 body weight), the blood glucose at an interval of 30 min till 120 min was measured from the blood collected from tail puncture. [ 43 ]…”