A Physical Map at 1p31 Encompassing the Acute Insulin Response Locus and the Leptin Receptor

Thompson, David V.; Sutherland, Jeff; Apel, Warren; Ossowski, Victoria

doi:10.1006/geno.1996.4504

Cited by 12 publications

(9 citation statements)

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“…Recently, an approximately 9-Mb YAC contig surrounding D1S198 was constructed (Thompson et al, 1997) and searched for candidate genes. Both the phosphodiesterase 4B gene (PDE4B) and the leptin receptor gene (LEPR) were found in the 9-Mb contig proximal of D1S98 and suggested as possible candidate genes.…”

Section: Discussionmentioning

confidence: 99%

“…genetics.soton.ac.uk/public_html/). Thompson et al (1997) constructed an approximately 9-Mb YAC contig surrounding the short tandem repeat marker D1S198, which shows linkage to AIR on chromosome 1. We chose four overlapping YACs (895B12, 930F4, 765B6, and 903C6) from that contig, which included the marker D1S198, the phosphodiesterase 4B (PDE4B) gene, or the leptin receptor (LEPR) gene.…”

Section: Radiation Hybrid Mappingmentioning

confidence: 99%

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Identification of INSL5, a New Member of the Insulin Superfamily

et al. 1999

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Section: Discussionmentioning

confidence: 99%

Section: Radiation Hybrid Mappingmentioning

confidence: 99%

Identification of INSL5, a New Member of the Insulin Superfamily

et al. 1999

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“…Determining a primary effect of leptin on insulin secretion will, however, require further investigation. In Pima Indians, a genetic linkage has been reported between measures of AIR to an intravenous glucose challenge and a locus which encompasses the leptin receptor indicating a potential role of leptin action in controlling AIR in this ethnic group (31).…”

Section: Journal Of Endocrinology (1999) 140mentioning

confidence: 99%

Analysis of the relationship between fasting serum leptin levels and estimates of beta-cell function and insulin sensitivity in a population sample of 380 healthy young Caucasians

Echwald

Clausen

Hansen

et al. 1999

European Journal of Endocrinology

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Objective: Circulating leptin levels correlate positively with the degree of obesity and prolonged hyperinsulinaemia increases serum leptin levels. Moreover, insulin secreting b-cells express functional leptin receptors indicating a functional relationship between leptin and insulin. The aim of this study was to examine the relationship between fasting serum leptin levels and measures of insulin sensitivity and b-cell function in a population-based sample of 380 young healthy Caucasians. Design and Methods: Multiple regression analysis was employed to analyse the relationship between fasting serum leptin levels and levels of fasting serum insulin, insulin sensitivity index and acute insulin response (AIR) in a population-based study of 380 young healthy Caucasians who underwent a combined intravenous glucose and tolbutamide tolerance test. Results and Conclusion: Serum leptin levels were positively correlated to measures of adiposity and were 3.2 times higher in women than in men (P < 0.00001). In multiple regression analyses adjusting for age, percentage body fat, waist circumference and maximal aerobic capacity, a significant positive correlation was observed between the fasting serum leptin concentrations and both fasting serum insulin levels (P < 0.0001) and AIR (P = 0.014) for women. No significant interrelation of these variables was found in men. However, for both genders a significant negative correlation was observed between fasting serum leptin levels and measures of insulin sensitivity index (P = 0.007).

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“…In contrast to congenital leptin deficiency, the majority of obese individuals have higher leptin concentrations than lean individuals and are leptin resistant (Considine et al 1996a;Moon et al 2011). Hyperleptinemia in humans can be due to mutations at highly conserved positions of the extracellular domain of the leptin receptor gene (Chung et al 1997;Francke et al 1997; Thompson et al 1997;Clément et al 1998). In 1966, Hummel et al described a spontaneous mutation in a C57BL/Ks mouse colony that provoked hyperphagia, decreased energy expenditure and obesity, fasting hyperglycemia increasing with age and increase in plasma insulin and leptin concentration (Hummel et al 1966;Coleman and Hummel 1967;Frederich et al 1995;Chen et al 1996;Chua et al 1996; Lee et al 1996;Madiehe et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice

et al. 2015

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Genetic predisposition and environmental challenges interact to determine individual vulnerability to obesity and type 2 diabetes. We previously established a mouse model of chronic subordination stress-induced hyperphagia, obesity, metabolic like-syndrome and insulin resistance in the presence of a high-fat diet. However, it remains to be established if social stress could also aggravate glucose intolerance in subjects genetically predisposed to develop obesity and type 2 diabetes. To answer this question, we subjected genetically obese mice due to deficiency of the leptin receptor (db/db strain) to chronic subordination stress. Over five weeks, subordination stress in db/db mice led to persistent hyperphagia, hyperglycemia and exacerbated glucose intolerance altogether suggestive of an aggravated disorder when compared to controls. On the contrary, body weight and fat mass were similarly affected in stressed and control mice likely due to the hyperactivity shown by subordinate mice. Stressed db/db mice also showed increased plasma inflammatory markers. Altogether our results suggest that chronic stress can aggravate glucose intolerance but not obesity in genetically predisposed subjects on the basis of a disrupted leptin circuitry.

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A Physical Map at 1p31 Encompassing the Acute Insulin Response Locus and the Leptin Receptor

Cited by 12 publications

References 0 publications

Identification of INSL5, a New Member of the Insulin Superfamily

Identification of INSL5, a New Member of the Insulin Superfamily

Analysis of the relationship between fasting serum leptin levels and estimates of beta-cell function and insulin sensitivity in a population sample of 380 healthy young Caucasians

Chronic stress aggravates glucose intolerance in leptin receptor-deficient (db/db) mice

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