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Sci Rep. 2018 Nov 19;8(1):17037. doi: 10.1038/s41598-018-35071-6.

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

Author information

1
Department of Molecular Biology, Cardiac Hypertrophy Laboratory, School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, Tamil Nadu, India.
2
DST Unit of Nanoscience & TUE, Department of Chemistry, Indian Institute of Technology, Chennai-600 036, Tamilnadu, India.
3
Department of Zoology, Madras Christian College, Chennai-600 059, Tamilnadu, India.
4
Center for Molecular and Translational Medicine, Georgia State University, Atlanta, GA, 30303, USA.
5
Institut de la Santé et de la Recherche Médicale, U1213, Lyon, 69372, France.
6
Université de Lyon, Lyon, 69008, France.
7
Université Lyon 1, Villeurbanne, 69622, France.
8
NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital and Imperial College, London, United Kingdom.
9
Department of Biochemistry, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, Tamil Nadu, India.
10
Department of Molecular Biology, Cardiac Hypertrophy Laboratory, School of Biological Sciences, Madurai Kamaraj University, Madurai-625 021, Tamil Nadu, India. subbiahr@nrcbsmku.org.

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.

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