Plasma Adrenomedullin Levels in Patients with Non-Insulin Dependent Diabetes Mellitus: Close Relationships with Diabetic Complications.

Nakamura, Tomoatsu; Honda, Kazuo; Ishikawa, San‐e; Kïtamura, Kazuo; Eto, Tanenao; Saito, Toshikazu

doi:10.1507/endocrj.45.241

Cited by 44 publications

(32 citation statements)

References 19 publications

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“…The insulin-resistant state that inexorably develops during obesity could be the source of the observed plasmatic adrenomedullin upregulation in diabetic patients (Fig. 7) (8,9,23). This is in accordance with the fact that insulin failed to inhibit adrenomedullin expression in obese and insulin-resistant ZDF rat adipocytes (Fig.…”

Section: Discussionsupporting

confidence: 77%

Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin

et al. 2007

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We generated preadipocyte cell lines impaired in adrenomedullin production through integration of an adrenomedullin small interfering RNA expression vector. The reduction of adrenomedullin synthesis strongly accelerated adipose differentiation. These results were bolstered when overexpression of active adrenomedullin peptide led to delayed differentiation. Therefore, we propose that adrenomedullin is an antiadipogenic factor. Moreover, we checked whether insulin, a proadipogenic factor, regulates expression of adrenomedullin. We observed that insulin had an inhibitory effect on adrenomedullin expression in isolated human adipocyte cells. This response was dose dependent and was reversed by resistin, a new anti-insulin agent. We quantified circulating adrenomedullin in healthy obese patients and observed a threefold increase of adrenomedullin compared with lean patients. Furthermore, adrenomedullin plasma levels are negatively correlated to plasma insulin levels in these obese patients. The insulin inhibitory response was also observed in vivo in SpragueDawley rats but not in the insulin-resistant Zucker rat, suggesting that adrenomedullin expression is upregulated in insulin-resistant adipose cells. Using adrenomedullin promoter-luciferase reporter gene constructs, we have shown that the adrenomedullin response to insulin is mediated by insulin-responsive elements. These findings provide new insight into fat mass development and the relationship between obesity and elevated circulating adrenomedullin levels in diabetic patients. Diabetes 56: 553-563, 2007

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Section: Discussionsupporting

confidence: 77%

Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin

et al. 2007

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“…Higher plasma levels of ADM or of MR-proADM were observed in patients with diabetic nephropathy than in patients without nephropathy in small cross-sectional Japanese and Chinese studies (25,26). However, no independent association was observed with the incidence of new cases of albuminuria in a larger Dutch study (ZODIAC) with a median follow-up of 5.6 years (27).…”

Section: Discussionmentioning

confidence: 90%

“…Epidemiological data on ADM and diabetic nephropathy are scarce (25)(26)(27). Based on what is known of the physiological effects of the peptide, we hypothesized that ADM may have a nephroprotective effect in diabetes.…”

mentioning

confidence: 99%

Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes

et al. 2015

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Production of adrenomedullin (ADM), a vasodilator peptide, increases in response to ischemia and hypoxia in the vascular wall and the kidney. This may be an adaptive response providing protection against organ damage. We investigated the hypothesis that ADM has a nephroprotective effect in two prospective cohorts of patients with type 2 diabetes recruited in France. The highest tertile of plasma MR-proADM (a surrogate for ADM) concentration at baseline was associated with the risk of renal outcomes (doubling of plasma creatinine concentration and/or progression to end-stage renal disease) during follow-up in both cohorts. Four SNPs in the ADM gene region were associated with plasma MR-proADM concentration at baseline and with eGFR during follow-up in both cohorts. The alleles associated with lower eGFR were also associated with lower plasma MR-proADM level. In conclusion, plasma MR-proADM concentration was associated with renal outcome in patients with type 2 diabetes. Our data suggest that the ADM gene modulates the genetic susceptibility to nephropathy progression. Results are consistent with the hypothesis of a reactive rise of ADM in diabetic nephropathy, blunted in risk alleles carriers, and with a nephroprotective effect of ADM. A possible therapeutic effect of ADM receptor agonists in diabetic renal disease would be worth investigating.

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“…These data suggest that AM is involved in the negative regulation of insulin secretion in an autocrine/paracrine manner. Furthermore, several clinical studies have reported that plasma AM concentrations are elevated in patients with diabetes (4,5,27). In fact, it has been shown that AM infusion increased plasma glucose levels in a diabetic rat model, whereas administration of anti-AM antibody had the opposite effect and improved postprandial recovery (21).…”

Section: Discussionmentioning

confidence: 99%

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

Fukai

Yoshimoto

Sugiyama

et al. 2005

American Journal of Physiology-Endocrinology and Metabolism

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.-Adrenomedullin (AM) expressed by and secreted from a variety of cells plays pluripotent roles in an autocrine/paracrine fashion. The present study was undertaken to explore the expression of AM and its receptor genes in adipose tissues, their changes during the development of obesity, and the process of preadipocyte differentiation. Both mature adipocytes and stromal vascular cells constituting adipose tissue expressed AM transcript. AM and its receptor component [calcitonin receptor-like receptor and receptor activitymodifying protein-2 (CRLR/RAMP2)] mRNAs were expressed in a variety of rat adipose tissues, including epididymal, mesenteric, retroperitoneal, and subcutaneous adipose tissue. AM mRNA levels in rat and human epididymal adipose tissue were about one-tenth of those in the kidney. Steady-state mRNA levels of AM and CRLR/ RAMP2 in epididymal, mesenteric, and retroperitoneal adipose tissues in rats fed a high-fat diet for 4 wk were far greater than those in rats with normal diet accompanied by increased plasma AM levels, whereas steady-state AM mRNA levels conversely decreased in other organs, such as kidney and liver. AM mRNA expressed in a mouse preadipocyte cell line (3T3-L1) transiently decreased by day 3, returned to basal level by day 6, and then increased by day 9 during preadipocyte differentiation, which paralleled AM secretion from the cells. However, the addition of either exogenous AM or AM receptor antagonist calcitonin gene-related peptide-(8 -37), to block endogenous AM did not affect lipid droplet accumulation during preadipocyte differentiation. The present study demonstrates for the first time that AM and its receptor component (CRLR/RAMP2) mRNAs were concomitantly expressed in various adipose tissues, whose tissuespecific upregulation was induced during the development of obesity. These data suggest that AM may act as a new member of adipokines, although its functional role, as well as its pathophysiological significance in obesity, remains to be determined. adipocyte; obesity; 3T3-L1 cells

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Plasma Adrenomedullin Levels in Patients with Non-Insulin Dependent Diabetes Mellitus: Close Relationships with Diabetic Complications.

Cited by 44 publications

References 19 publications

Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin

Adrenomedullin Inhibits Adipogenesis Under Transcriptional Control of Insulin

Plasma Adrenomedullin and Allelic Variation in the ADM Gene and Kidney Disease in People With Type 2 Diabetes

Concomitant expression of adrenomedullin and its receptor components in rat adipose tissues

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