Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension - PubMed (original) (raw)
Review
. 1998 Nov;188(1-2):129-36.
Affiliations
- PMID: 9823018
Review
Nutritional and endocrine modulation of intracellular calcium: implications in obesity, insulin resistance and hypertension
M B Zemel. Mol Cell Biochem. 1998 Nov.
Abstract
Regulation of intracellular Ca2+ ([Ca2+]i) plays a key role in obesity, insulin resistance and hypertension, and [Ca2+]i disorders may represent a fundamental factor linking these three conditions. We have shown insulin to be a direct vasodilator, attenuating voltage-gated Ca2+ influx and stimulating Ca(2+)-ATPase transcription via a glucose-6-phosphate response element. These result in a net decrease in [Ca2+]i and thereby decrease vascular resistance, while these effects are blunted in insulin resistance, leading to increased vascular resistance. Consistent with this concept, pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. While insulin regulates [Ca2+]i, Ca2+ also regulates insulin signaling, as increasing [Ca2+]i impairs insulin signaling in some systems, possibly due to Ca2+ inhibition of insulin-regulated dephosphorylation. Finally, in recent studies of the mouse agouti gene, we have also demonstrated increased [Ca2+]i to play a key role in adipocyte lipogenesis, as follows. We have found dominant agouti mutants to exhibit increased [Ca2+]i in most tissues, leading to increased vascular reactivity and insulin resistance in vascular smooth muscle and skeletal muscle cells, respectively. Further, we have found recombinant agouti protein to directly increase [Ca2+]i in a variety of cells, including murine and human adipocytes, and to stimulate both the expression and activity of adipocyte fatty acid synthase and increase triglyceride accumulation in a Ca(2+)-dependent manner. These effects can be mimicked by stimulation of Ca2+ influx and blocked by Ca2+ channel inhibition, while treatment of mice with a Ca2+ antagonist attenuates agouti-induced obesity. Since humans express agouti in adipose tissue, it may similarly exert paracrine effects on [Ca2+]i and thereby stimulate de novo lipogenesis and promote obesity. Thus, Ca2+ signaling represents a target for therapeutic intervention in obesity as well as hypertension and insulin resistance.
Similar articles
- The agouti gene product inhibits lipolysis in human adipocytes via a Ca2+-dependent mechanism.
Xue B, Moustaid-N, Wilkison WO, Zemel MB. Xue B, et al. FASEB J. 1998 Oct;12(13):1391-6. FASEB J. 1998. PMID: 9761782 - Agouti regulation of intracellular calcium: role of melanocortin receptors.
Kim JH, Kiefer LL, Woychik RP, Wilkison WO, Truesdale A, Ittoop O, Willard D, Nichols J, Zemel MB. Kim JH, et al. Am J Physiol. 1997 Mar;272(3 Pt 1):E379-84. doi: 10.1152/ajpendo.1997.272.3.E379. Am J Physiol. 1997. PMID: 9124542 - Cellular calcium and magnesium metabolism in the pathophysiology and treatment of hypertension and related metabolic disorders.
Resnick LM. Resnick LM. Am J Med. 1992 Aug 31;93(2A):11S-20S. doi: 10.1016/0002-9343(92)90290-r. Am J Med. 1992. PMID: 1387762 Review. - Calcium modulation of hypertension and obesity: mechanisms and implications.
Zemel MB. Zemel MB. J Am Coll Nutr. 2001 Oct;20(5 Suppl):428S-435S; discussion 440S-442S. doi: 10.1080/07315724.2001.10719180. J Am Coll Nutr. 2001. PMID: 11603653 Review.
Cited by
- Mechanisms Linking Vitamin D Deficiency to Impaired Metabolism: An Overview.
Mohd Ghozali N, Giribabu N, Salleh N. Mohd Ghozali N, et al. Int J Endocrinol. 2022 Jul 6;2022:6453882. doi: 10.1155/2022/6453882. eCollection 2022. Int J Endocrinol. 2022. PMID: 35859985 Free PMC article. Review. - Dietary Micronutrient Status and Relation between Micronutrient Intakes and Overweight and Obesity among Non-Pregnant and Non-Lactating Women Aged 18 to 49 in China.
Ju L, Wei X, Yu D, Fang H, Cheng X, Piao W, Guo Q, Xu X, Li S, Cai S, Zhao L. Ju L, et al. Nutrients. 2022 Apr 30;14(9):1895. doi: 10.3390/nu14091895. Nutrients. 2022. PMID: 35565860 Free PMC article. - Beta-Cell Adaptation to Pregnancy - Role of Calcium Dynamics.
Pretorius M, Huang C. Pretorius M, et al. Front Endocrinol (Lausanne). 2022 Mar 25;13:853876. doi: 10.3389/fendo.2022.853876. eCollection 2022. Front Endocrinol (Lausanne). 2022. PMID: 35399944 Free PMC article. Review. - Interaction between Dietary Fat Intake and Metabolic Genetic Risk Score on 25-Hydroxyvitamin D Concentrations in a Turkish Adult Population.
Isgin-Atici K, Alathari BE, Turan-Demirci B, Sendur SN, Lay I, Ellahi B, Alikasifoglu M, Erbas T, Buyuktuncer Z, Vimaleswaran KS. Isgin-Atici K, et al. Nutrients. 2022 Jan 17;14(2):382. doi: 10.3390/nu14020382. Nutrients. 2022. PMID: 35057563 Free PMC article. - Prevalence of Metabolic Syndrome in Children and Adolescents with Type 1 Diabetes Mellitus and Possibilities of Prevention and Treatment: A Systematic Review.
Grabia M, Markiewicz-Żukowska R, Socha K. Grabia M, et al. Nutrients. 2021 May 23;13(6):1782. doi: 10.3390/nu13061782. Nutrients. 2021. PMID: 34071142 Free PMC article.
References
- Am J Physiol. 1991 Mar;260(3 Pt 1):E459-63 - PubMed
- Proc Natl Acad Sci U S A. 1995 May 23;92(11):4728-32 - PubMed
- Diabetes. 1981 Mar;30(3):219-25 - PubMed
- Metabolism. 1995 Mar;44(3):315-9 - PubMed
- Physiol Genomics. 1999 Jul 15;1(1):11-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Miscellaneous