Skip to main content
Log in

The effect of Gc genotype on fasting insulin level in Dogrib Indians

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Summary

The metabolically active form of vitamin D, 1,25-(OH)2D3, is involved in the regulation of insulin level. Because the serum group-specific component (Gc) binds vitamin D, it is worth knowing whether differences in basal insulin levels are associated with Gc genotype. Such differences would warrant further investigation to clarify whether selection maintains Gc polymorphism through differential risk of Gc genotypes to diseases that involve insulin. Blood samples were collected in a study designed to address issues in the etiology of non-insulin-dependent diabetes mellitus in Amerindians. Fasting insulin levels and Gc genotype (including subtypes of Gc 1) were determined for 144 adult Dogrib Indians of the Northwest Territories, Canada. Hierarchical regression of log10 transformed fasting insulin on age and adiposity within each sex showed that age had no effect on insulin level, but adiposity as measured by the body mass index (BMI) had a very highly significant effect. Analysis of covariance of log10 fasting insulin by sex, by Gc genotype and with adjustment for the effects of the covariate, BMI, was very highly significant. All interaction terms in the model were nonsignificant. The only variable that had a significant effect after adjustment for the BMI was Gc genotype (F4,133=3.71; P=0.007). Covariance analysis was repeated on a subset of the sample (124 people). The reduced data set excluded all individuals who had, on at least one occasion, abnormal response to oral glucose challenge [impaired glucose tolerance (IGT) or noninsulin-dependent diabetes mellitus (NIDDM)]. Again, after correction for the effects of the BMI, only Gc genotype had a significant effect on fasting insulin level (F4,113=2.61; P=0.040). Homozygotes for Gc 1F-1F had the lowest measures of fasting insulin.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aronoff SL, Bennett PH, Gorden P, Rushforth N, Miller M (1977) Unexplained hyperinsulinemia in normal and “prediabetic” Pima Indians compared with normal Caucasians. Diabetes 26:827–840

    Google Scholar 

  • Bagdade JD, Bierman EL, Porte D Jr (1967) The significance of basal insulin levels in the evaluation of the insulin response to glucose in diabetic and nondiabetic subjects. J Clin Invest 46:1549–1557

    Google Scholar 

  • Bennett PH (1982) The epidemiology of diabetes mellitus. In: Blodoff BN, Bleicher SI (eds) Diabetes mellitus and obesity. Williams & Wilkins, Baltimore, pp 387–399

    Google Scholar 

  • Berg K, Aarseth S, Lundevall J, Reinskou T (1967) Blood groups and genetic serum types in diabetes mellitus. Diabetologia 3:30–34

    Google Scholar 

  • Bouillon R, Van Baelen H, DeMoor P (1977) The measurement of the vitamin D-binding protein in human serum. J Clin Endocrinol Metab 45:225–231

    Google Scholar 

  • Christakos S, Norman AW (1981) Studies on the mode of action of calciferol. XXXIII. Biochemical characterization of 1,25-dihydroxyvitamin D3 receptors in chick pancreas and kidney cytosol. Endocrinology 108:140–149

    Google Scholar 

  • Clark SA, Stumpf WE, Sar M (1981) Effect of 1,25 dihydroxyvitamin D3 on insulin secretion. Diabetes 30:382–386

    Google Scholar 

  • Cleve H (1966) Die Verteilung der Gc-Typen und Gc-Allele bei Kranken mit Diabetes mellitus und chronischer Polyarthritis. Humangenetik 2:355–362

    Google Scholar 

  • Constans J, Viau M, Cleve H, Jaeger G, Quilici JC, Palisson MJ (1978) Analysis of Gc polymorphism in human populations by isoelectric focussing in polyacrylamide gels. Demonstration of subtypes of the Gc1 alleles and of additional Gc variants. Hum Genet 41:53–60

    Google Scholar 

  • Daiger SP, Cavalli-Sforza LL (1977) Detection of genetic variation with radioactive ligands. II. Genetic variants of vitamin D-labelled group specific component (Gc) proteins. Am J Hum Genet 29:593–604

    Google Scholar 

  • Daiger SP, Schanfield MS, Cavalli-Sforza LL (1977) Group-specific component (Gc) proteins bind vitamin D and vitamin D metabolites. Proc Natl Acad Sci USA 72:2076–2080

    Google Scholar 

  • Daiger SP, Miller M, Romeo G, Parsons M, Cavalli-Sforza LL (1978) Vitamin D-binding protein in Williams syndrome. N Engl J Med 298:687–688

    Google Scholar 

  • Daiger SP, Miller M, Chakraborty R (1984) Heritability of quantitative variation of the group-specific component (Gc) locus. Am J Hum Genet 36:663–676

    Google Scholar 

  • Gedik O, Akalin S (1986) Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man. Diabetologia 29: 142–145

    Google Scholar 

  • Genuth SM, Bennett PH, Miller M, Burch TA (1967) Hyperinsulinism in obese diabetic Pima Indians. Metabolism 16:1010–1015

    Google Scholar 

  • Haddad JG Jr, Walgate J (1976) 25-Hydroxyvitamin D transport in human plasma. J Biol Chem 251:4803–4809

    Google Scholar 

  • Hull CH, Nie NH (1981) SPSS update 7–9. McGraw-Hill, Toronto New York

    Google Scholar 

  • Jörgensen G, Hopfer A (1966) Die Verteilung der Gc-Phänotypen und Gc-Allele bei einigen Krankheiten (Diabetes mellitus, Leberparenchymschaden, Psoriasis vulgaris). Humangenetik 3:273–276

    Google Scholar 

  • Kadowaki S, Norman AW (1985) Demonstration that the vitamin D metabolite 1,25(OH)2-vitamin D3, and not 24R,25(OH)2-vitamin D3, is essential for normal insulin secretion in the perfused rat pancreas. Diabetes 34:315–320

    Google Scholar 

  • Kirk RL, Serjeantson SW, Zimmet P (1982) Genes and diabetes in the Pacific. In: Mimura G, Baba S, Goto Y, Köbberling J (eds) Clinicogenetic genesis of diabetes mellitus. Excerpta Medica, Amsterdam, pp 34–41

    Google Scholar 

  • Kirk RL, Serjeantson SW, King H, Zimmet P (1985) The genetic epidemiology of diabetes mellitus. In: Chakraborty R, Szathmary EJE (eds) Diseases of complex etiology in small populations. Liss, New York, pp 105–118

    Google Scholar 

  • Kreisberg RA, Boshell Br, DiPlacido J, Roddam RF (1967) Insulin secretion in obesity. N Engl J Med 276:314–319

    Google Scholar 

  • Linder MC (1986) Nutrition and metabolism of vitamins. In: Linder MC (ed) Nutritional biochemistry and metabolism. Elsevier, New York Amsterdam, pp 69–132

    Google Scholar 

  • Mohan V, Sharp PS, Cloke HR, Burrin JM, Schumer B, Kohner EM (1986) Serum immunoreactive insulin responses to a glucose load in Asian Indian and European Type 2 (non-insulin-dependent) diabetic patients and control subjects. Diabetologia 29:235–237

    Google Scholar 

  • National Diabetes Data Group (1979) Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039–1057

    Google Scholar 

  • Nie NH, Hull CH, Jenkins JG, Steinbrenner K, Bent DH (1975) SPSS, 2nd edn. McGraw-Hill, Toronto New York

    Google Scholar 

  • Norman AW, Frankel BJ, Heldt AM, Grodsky GM (1980) Vitamin D deficiency inhibits pancreatic secretion of insulin. Science 209: 823–825

    Google Scholar 

  • Nyomba BL, Bouillon R, De Moor P (1984) Influence of vitamin D status on insulin secretion and glucose tolerance in the rabbit. Endocrinology 115:191–197

    Google Scholar 

  • Nyomba BL, Auwerx J, Bormans V, Peeters TL, Pelemans W, Reynaert J, Bouillon R, Vantrappen G, De Moor P (1986) Pancreatic secretion in man with subclinical vitamin D deficiency. Diabetologia 29:34–38

    Google Scholar 

  • Olson RE (1982) Vitamin D and insulin (editorial). Nutrit Rev 40: 221–222

    Google Scholar 

  • Savage PJ, Dippe SE, Bennett PH, Gorden P, Roth J, Rushforth NB, Miller M (1975) Hyperinsulinemia and hypoinsulinemia. Insulin responses to oral carbohydrate over a wide spectrum of glucose tolerance. Diabetes 24:362–368

    Google Scholar 

  • Scholz W, Knussmann R, Daweke H (1975) Distribution of blood and serum protein group characteristics in patients with diabetes. Diabetologia 11:77–82

    Google Scholar 

  • Szathmary EJE (1985) The search for genetic factors controlling plasma glucose levels in Dogrib Indians. In: Chakraborty R, Szathmary EJE (eds) Diseases of complex etiology in small populations. Liss, New York, pp 199–226

    Google Scholar 

  • Szathmary EJE (1987) Diabetes in arctic and subarctic populations undergoing acculturation. Collegium Anthropologicum (in press)

  • Szathmary EJE, Holt N (1983) Hyperglycemia in Dogrib Indians of the Northwest Territories, Canada. Association with age and a centripetal distribution of body fat. Hum Biol 55:493–515

    Google Scholar 

  • Szathmary EJE, Ferrell RE, Gershowitz H (1983) Genetic differentiation in Dogrib Indians: serum protein and erythrocyte enzyme variation. Am J Phys Anthropol 62:249–254

    Google Scholar 

  • Szathmary EJE, Ritenbaugh C, Goodby CS (1987) Dietary change and plasma glucose levels in an Amerindian population undergoing cultural transition. Soc Sci Med (in press)

  • Van Baelen H, Bouillon R, De Moor P (1978) The heterogeneity of human Gc-globulin. J Biol Chem 253:6344–6345

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Szathmary, E.J.E. The effect of Gc genotype on fasting insulin level in Dogrib Indians. Hum Genet 75, 368–372 (1987). https://doi.org/10.1007/BF00284110

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00284110

Keywords

Navigation