• Subhash T. Kumbhar CRD, PRIST University, Thanjavur, TN, India & Indira College of Pharmacy, Pune, MS, India
  • Hemant D. Une YB Chavan College of Pharmacy, Aurangabad, MS, India.
  • Anagha M. Joshi Indira College of Pharmacy, Pune, MS, India
  • Pralhad B. Wangikar PRADO Preclinical Pvt. Ltd, Ravet, Pune, MS, India.


Objective: This study evaluated the toxic effect of simultaneously injected normal doses of caffeine and nicotine in diabetic lab animals.

Methods: A study was conducted for three weeks in seven rat groups (n=6); viz. first non-diabetic group treated with caffeine (20 mg/kg, ip) twice daily, second with nicotine (0.4 mg/kg, ip) twice daily and third with both treatments simultaneously; whereas other three groups treated in the same way but inducing diabetes; and employing the seventh group as diabetic control. Type 2 diabetes was induced by high fatty diet prior for two weeks and a single streptozotocin injection on 1th day of study in all diabetic groups. Blood and urine samples were collected weekly to estimate blood parameters. Animals were sacrificed, and organs were collected for histopathology analysis.

Results: Most blood parameters showed a rapid increase in diabetes in co-addiction group compared with their single addiction or non-addiction control groups. Caffeine-nicotine co-addiction group showed about 60-80 mg/dl (p<0.05) rise in serum glucose, 15-20 U/l in AST (p<0.01), 80-100 U/l in ALT (p<0.01), 20-30 mg/dl in Urea (p<0.01), 02 mg/dl in creatinine (p<0.05), 12-15 mg/dl (p<0.01) in LDL-C, 6-9 mg/dl in VLDL-C (p<0.01) and 60-90 mg/dl in TC levels (p<0.01) when compared with non-addicted diabetic control. There was a significant reduction in HDL-C (p<0.01) while the less significant rise in triglycerides in the case of co-addiction as compared to non-addiction diabetic control group. Histopathology results exhibited moderate to severe tissue damage in agreement with clinical biochemistry results.

Conclusion: Nicotine-caffeine co-addiction harms exceptionally more in type 2 diabetes greater than their single addiction or non-addiction.

Keywords: Streptozotocin, Caffeine, Nicotine, Type 2 diabetes, Insulin resistance


Download data is not yet available.


1. Dhaliwall C, Erinmacpherson, Richardson J. Effectiveness of telephone-delivered interventions for increasing physical activity levels in persons with type 2 diabetes or hypertension: a systematic review. J Crit Rev 2015;2:06-11.
2. Malini P, Kanchana G, Rajadurai M. Antidiabetic efficacy of ellagic acid in streptozotocin­induced diabetes mellitus in albino Wistar rats. Asian J Pharm Clin Res 2011;4:125-8.
3. Van Dijk AE, Olthof MR, Meeuse JC, Seebus E, Heine RJ, Van Dam RM. Acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. Diabetes Care 2009;32:1023–5.
4. Egawa T, Hamada T, Kameda N, Karaike K, Ma X, Masuda S, et al. Caffeine acutely activates 5’adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles. Metabolism 2009;58:1609–17.
5. Akiba T, Yaguchi K, Tsutsumi K, Nishioka T, Koyama I, Nomura M, et al. Inhibitory mechanism of caffeine on insulin-stimulated glucose uptake in adipose cells. Biochem Pharmacol 2004; 68:1929–37.
6. Kashani AE, Yaghmaei P, Larijani B, Ebrahim HA. Xanthine derivatives as activators of alpha-amylase: a hypothesis on a link with the hyperglycemia induced by caffeine. Obesity Res Clin Practice 2013;7:e487–93.
7. Bergman BC, Perreault L, Hunerdosse D, Kerege A, Playdon M, Samek AM, et al. Novel and reversible mechanisms of smoking-induced insulin resistance in humans. Diabetes 2012;61:3156–66.
8. Li W, Hui R. Cigarette smoking induces insulin resistance: partly via ASP–C5L2 pathway? Biosci Hypotheses 2009;2:267–9.
9. Rajan AK, Kousalya K, Senthil NB, Valentina P. An outlook on the mechanisms of drug interactions with other drugs, fruits, herbs and their preventive measures. Asian J Pharm Clin Res 2016;9:10-8.
10. Skovsø S. Modeling types 2 diabetes in rats using high-fat diet and streptozotocin. J Diabetes Invest 2014;5:349–58.
11. Srinivasan K, Ramarao P. Animal models in type 2 diabetes research: an overview. Indian J Med Res 2007;125:451–72.
12. Divi SM, Bellamkonda R, Dasireddy SK. Valuation of the antidiabetic and antihyperlipidemic potential of aqueous extract of Moringa oleifera in fructose-fed insulin resistant and STZ induced diabetic wistar rats: a comparative study. Asian J Pharm Clin Res 2012;5:67-72.
13. Kim Y, Keogh JB, Clifton PM. Polyphenols and glycemic control. Nutrients 2016;8:17.
14. Ihm SH, Jang SW, Kim OR, Chang K, Oak MH, Lee JO. Decaffeinated green tea extract improves hypertension and insulin resistance in a rat model of metabolic syndrome. Atherosclerosis 2012;224:377–83.
15. Lane JD, Barkauskas CE, Surwit RS, Feinglos MN. Caffeine impairs glucose metabolism in type 2 diabetes. Diabetes Care 2004;27:2047–8.
16. Beaudoin MS, Robinson LE, Graham TE. An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men. J Nutr 2011;141:574–81.
17. Van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005;294:97–104.
18. Morgan TM, Crawford L, Stoller A, Toth D, Yeo KTJ, Baron JA. Acute effects of nicotine on serum glucose-insulin growth hormone and cortisol in healthy smokers. Metabolism 2004;53:578–82.
19. Chiolero A, Faeh D, Paccaud F, Cornuz J. Consequences of smoking for body weight, body fat distribution, and insulin resistance. Am J Clin Nutr 2008;87:801–9.
20. Eliasson B, Taskinen MR, Smith U. Long-term use of nicotine gum is associated with hyperinsulinemia and insulin resistance. Circulation 1996;94:878–81.
21. Wu Y, Song P, Zhang W, Liu J, Dai X, Liu Z, et al. Activation of AMPK [alpha] 2 in adipocytes is essential for nicotine-induced insulin resistance in vivo. Nat Med 2015;21:373–82.
22. Assali AR, Beigel Y, Schreibman R, Shafer Z, Fainaru M. Weight gain and insulin resistance during nicotine replacement therapy. Clin Cardiol 1999;22:357–60.
23. Richardson JR, Pipkin JA, O’Dell LE, Nazarian A. Insulin resistant rats display enhanced rewarding effects of nicotine. Drug Alcohol Depend 2014;140:205–7.
24. Eliasson B1, Attvall S, Taskinen MR, Smith U. The insulin resistance syndrome in smokers is related to smoking habits. Arterioscler Thromb 1994;14:1946-50.
25. Matta S, Balfour D, Benowitz N, Boyd RT, Buccafusco J, Caggiula AR, et al. Guidelines on nicotine dose selection for in vivo research. Psychopharmacology (Berl) 2007;190:269–319.
26. Gupta M. Impact of meal replacement on the health status of type ii diabetes. Int J Curr Pharm Res 2014;6:79-82.
498 Views | 591 Downloads
How to Cite
Kumbhar, S. T., H. D. Une, A. M. Joshi, and P. B. Wangikar. “EXAGGERATION OF TYPE 2 DIABETES DUE TO CAFFEINE-NICOTINE CO-ADMINISTRATION: A STUDY IN RATS”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 8, no. 9, Sept. 2016, pp. 277-82, doi:10.22159/ijpps.2016.v8i9.13590.
Original Article(s)