Fasting hyperglycaemia, glucose intolerance and pancreatic islet necrosis in albino rats associated with subchronic oral aluminium chloride exposure

  • 12 Accesses


Exposure to aluminium is associated with altered glycaemia, but this effect in relation to glucose tolerance and pancreatic islet pathology requires validation. The study was aimed at assessing the glycaemic changes, glucose tolerance and islet morphology of albino rats during oral aluminium chloride exposure. Twenty male albino rats weighing 189–270 g were randomly divided into two equal groups. The control group was sham-treated with normal saline and the treated group was administered aluminium chloride solution (100 g/L) by gavage at 12.5% of LD50 (50 mg/kg) daily for 28 days. Fasting blood glucose (FBG) and postprandial blood glucose (PBG) concentrations after glucose gavage at 1 g/kg were estimated and the pancreatic islet tissues were examined for histopathological changes. The treatment caused significant (p < 0.05) time-dependent (r = 0.97) increases in FBG. Hyperglycaemic effect was estimated to be 28-day glycaemic increase of 61% and aggregate glycaemic increases of 44% and 53% between and within groups, respectively. Oral glucose tolerance was impaired judging by changes in PBG which indicated reduction of both intestinal absorption and clearance of blood glucose in treated group by 37% and 17%, respectively. Coagulative necrosis and 31% reduction (p < 0.05) in cell count of the pancreatic islet tissue were associated with the deranged circulatory glucose homeostasis in the treated group. In conclusion, aluminium loading seems to affect insulin production and action and may have a contributory role in diabetogenesis.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6


  1. Afridi HI, Talpur FN, Kazi TG, Brabazon D (2015) Effect of trace and toxic elements of different brands of cigarettes on the essential elemental status of Irish referent and diabetic mellitus consumers. Trace Elem Res 167(2):209–224

  2. Chen YW, Yang CY, Huang CF, Hung DZ, Leung YM, Liu SH (2009) Heavy metals, islet function and diabetes development. Islets 1(3):169–176

  3. EFSA (2008) Safety of aluminium from dietary intake. EFSA J 754:1–34

  4. Feng W, Cui X, Liu B, Liu C, Xiao Y, Lu W (2015) Association of urinary metal profiles with altered glucose levels and diabetes risk: a population-based study in China. PLoS One 10:e0123742

  5. Flores CR, Puga MP, Wrobel K, Sevilla MEG, Wrobel K (2011) Trace elements status in diabetes mellitus type 2: possible role of the interaction between molybdenum and copper in the progress of typical complications. Diabetes Res Clin Pract 91:333–341

  6. Gonzalez MA, Alvarez ML, Pisani GB (2007) Involvement of oxidative stress in the impairment in biliary secretory function induced by intraperitoneal administration of aluminum to rats. Biol Trace Elem Res 116(1):329–348

  7. Gorboulev V, Schürmann A, Vallon V, Kipp H, Jaschke A, Klessen D et al (2011) Na (+)-D-SGLT1 is pivotal for intestinal glucose absorption and glucose-dependent incretin secretion. Diabetes 61:187–196

  8. Igbokwe IO, Shamaki LS, Hamza H, Gidado A (1999) Fasting hyperglycaemia with oral glucose tolerance in acute Trypanosoma congolense infection of rats. Vet Parasitol 81:167–171

  9. Järup L (2003) Hazards of heavy metal contamination. Br Med Bull 68:167–182

  10. Johnson VJ, Kim SH, Sharma RP (2005) Aluminium-maltolate induces apoptosis and necrosis in neuro-2a cells: potential role for p53 signaling. Toxicol Sci 83(2):329–339

  11. Kellett G, Helliwell P (2009) The diffuse component of intestinal absorption is mediated by the glucose-induced recruitment of GLUT2 to the brush-border membrane. Biochem J 350:155–162

  12. Konda VR, Eerike M, Chary RP, Arunachalam R, Yeddula VR, Meti V, Devi TS (2017) Effect of aluminum chloride on blood glucose level and lipid profile in normal, diabetic and treated diabetic rats. Indian J Pharm 49:357–365

  13. Krasovskii GN, Vasukovich LY, Chariev OG (1979) Experimental study of biological effects of lead and aluminum following oral administration. Environ Health Perspect 30:47–51

  14. Mailloux RJ, Hamel R, Appanna VD (2006) Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes. J Biochem Mol Toxicol 20:198–208

  15. Mirhashemi SM, Aarabi MH (2011) To study various concentrations of magnesium and aluminium on amylin hormone conformation. Pak J Biol Sci 14(11):653–657

  16. Mirhashemi SM, Shahabaddin M-E (2011) Evaluation of aluminium, manganese, copper and selenium effects on human islets amyloid polypeptide hormone aggregation. Pak J Biol Sci 14(4):288–292

  17. Moshtaghie A, Ani M (1991) Interferance of aluminium with carbohydrate metabolism in male rats: a model study of dialysis patients. J Sci Islamic Republic of Iran 2(1,2):1–4

  18. Obukhova T, Budkar’ LN, Tereshina LG, Karpova EA (2015) [dissociation of disorders of carbohydrate and lipid metabolism in aluminum industry workers according to medical examination data] in Russian. Gig Sanit 94(2):67–69

  19. Reusche E, Lindner B, Arnholbt H (1994) Widespread aluminium deposition in extracerebral organ systems of patients with dialysis-associated encephalopathy. Virchows Arch 424:105–112

  20. Rheney CC, Kirk KK (2000) Performance of three blood glucose meters. Ann Pharmacother 34(3):317–321

  21. Russel C, Palmer JE, Boston RC, Wilkins PA (2007) Agreement between point-of-care glucometry, blood gas and laboratory-based measurement of glucose in an equine neonatal intensive care unit. J Vet Emerg Crit Care 17(3):236–242

  22. Serdar MA, Bakir F, Hasimi A, Celik T, Akin O, Kenar L, Aykut O, Yildirimkaya M (2009) Trace and toxic element patterns in nonsmoker patients with noninsulin-dependent diabetes mellitus, impaired glucose tolerance, and fasting glucose. Int J Diabetes Dev C 29:35–40

  23. van der Voet GB (1992) Interstinal absorption of aluminium. CIBA Found Symp 169:109–117

  24. Vignal C, Desreumaux P, Body-Malapel M (2016) Gut: an underestimated target organ for aluminium. Morphologie 100(329):75–84

  25. Wei H, Wang MD, Meng LX (2012) Laurel West aluminum industrial base residents trace element content in serum and its associated abnormal glucose metabolism (J). Mod Prev Med 4:065

  26. Wei X, Wei H, Yang D, Li D, Yang X, He M, Lin E, Wu B (2018) Effect of aluminum exposure on glucose metabolism and its mechanism in rats. Biol Trace Elem Res 186:450–456. First online 28 March 2018.

  27. Xu ZX, Fox S, Melethel L, Winderg I, Badr M (1990) Mechanism of aluminium-induced inhibition of hepatic glycolysis. J Pharmacol Exp Ther 254:301–305

  28. Xu Z-X, Zhang Q, Ma G-L, Chen C-H, He Y-M, Xu L-H, Zhang Y, Zhou G-R, Li Z-H, Yang H-J, Zhou P (2016, 2016) Influence of aluminium and EGCCG on fibrillation and aggregation of human islet amyloid polypeptide. J Diabetes Res:1867059, 14 pages.

  29. Zhou Y, Harris WR, Yokel RA (2008) The influence of citrate, maltolate and fluoride on the gastrointestinal absorption of aluminum at a drinking water-relevant concentration: a 26Al and 14C study. J Inorg Biochem 102:798–808

Download references


Technical assistance was provided by Bitrus Wampana and Tijani Aji Goni.

Funding information

Financial assistance was granted by the Council of the University of Maiduguri through a study fellowship to Ephraim Igwenagu.

Author information

Correspondence to Ephraim Igwenagu or Ikechukwu Onyebuchi Igbokwe.

Ethics declarations

Ethical compliance

The research was approved by the School of Postgraduate Studies Board of the University of Maiduguri, Maiduguri, Nigeria, and complied with institutional, national and international standards for research on laboratory animals.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Igwenagu, E., Igbokwe, I.O. & Egbe-Nwiyi, T.N. Fasting hyperglycaemia, glucose intolerance and pancreatic islet necrosis in albino rats associated with subchronic oral aluminium chloride exposure. Comp Clin Pathol 29, 75–81 (2020) doi:10.1007/s00580-019-03028-4

Download citation


  • Albino rats
  • Aluminium intoxication
  • Hyperglycaemia
  • Oral glucose intolerance
  • Pancreatic islet necrosis
  • Subchronic toxicity