Salivary Gland Hyperglycemic Factor: An Extrapancreatic Source of Glucagon-Like Material

Lawrence, A. M.; Tan, Song; Hojvat, Sally; Kirsteins, L.

doi:10.1126/science.63992

Cited by 82 publications

(46 citation statements)

References 20 publications

(11 reference statements)

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“…5, which is published as supporting information on the PNAS web site). Although it would seem surprising that a presumptive endocrine factor is strongly expressed in an exocrine gland, there have been numerous reports of other growth factors being expressed in salivary glands (15)(16)(17)(18)(19), and it has been shown that endocrine factors expressed after introduction of DNA into these glands are readily secreted into the bloodstream (20,21). Indeed, a body of opinion contends that salivary glands have a mixed exocrine and endocrine function (22)(23)(24).…”

Section: Resultsmentioning

confidence: 99%

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

Macdonald

Wortley

Gowen

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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We identified a glycoprotein hormone ␤-subunit (OGH, also called GPB5) that, as a heterodimer with the ␣-subunit GPA2, serves as a second ligand for the thyroid-stimulating hormone receptor. Mice in which the OGH gene is deleted (OGH ؊/؊ ) are indistinguishable from WT littermates in body weight, response to high-fat diet, metabolic parameters, body composition, and insulin tolerance. Mice engineered to transgenically globally overexpress OGH (OGH-TG) develop Ϸ2-fold elevations in their basal thyroid levels and weigh slightly less than WT littermates despite increased food intake because of an increase in their metabolic rates. Moreover, when OGH-TG mice are challenged with a high-fat diet, they gain significantly less weight and body fat than their WT littermates. The OGH-TG mice also have reduced blood glucose, insulin, cholesterol, and triglycerides. In contrast to other approaches in which the thyroid axis is activated, OGH-TG mice exhibit only minor changes in heart rate and blood pressure. Our findings suggest that constitutive low-level activation of the thyroid axis (via OGH or other means) may provide a beneficial therapeutic approach for combating diet-induced obesity.cholesterol ͉ metabolic rate ͉ thyroid T hyroid-stimulating hormone (TSH) and the TSH receptor (TSHR) are key proteins in the control of thyroid function. TSH synthesis and release is stimulated by hypothalamic TSHreleasing hormone (TRH) and is down-regulated (inhibited) by thyroid hormone in a classic endocrine negative-feedback loop. The specificity inherent in TSH resides in its unique ␤-subunit that heterodimerizes with a common ␣-subunit, which it shares with the other glycoprotein hormones [i.e., follicle-stimulating hormone (FSH), luteinizing hormone, and chorionic gonadotropin]. The primary physiological actions of TSH on the thyroid are stimulation of the synthesis and release of 3,5,3Ј,5Ј-tetraiodo-L-thyronine (T4) and 3,5,3Ј-triiodo-L-thyronine (T3) (together termed thyroid hormone) and promotion of thyroid growth; for example, it has been shown that thyroid development is arrested in mice with targeted disruption of the common ␣-subunit (1).Clinically, thyroid hormone is used primarily as a replacement therapy for the patients with hypothyroidism, and it has been considered as a possible therapy for weight reduction (because of its ability to increase metabolism and energy expenditures), for lowering cholesterol, and even to build bone (in osteoporosis). One of the major hurdles in this approach has been the cardiovascular toxicity observed after administration of the endogenous ligands T4 and T3 or nonselective thyroid hormone agonists. The two major subtypes of the thyroid hormone receptors that mediate these responses, TR␣ and TR␤, are the products of different genes and are also differentially processed to each yield two isoforms. It has been argued that modulation of heart rate and rhythm is mediated predominantly by activation of TR␣ 1 (2-4), and as a result, recent pharmaceutical research efforts have focused on develop...

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Section: Resultsmentioning

confidence: 99%

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

Macdonald

Wortley

Gowen

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

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“…nerve growth factor, epidermal growth factor [5,6]. Submaxillary salivary glands might contain glucagon-like precursor material [ 1,2]. Our investigation demonstrated that 3 protein fractions from submaxillary salivary glands of rats are able to release FFA and glycerol from rat adipose tissue during the in vitro incubation.…”

Section: Resultsmentioning

confidence: 78%

“…Glucagon-like protein fractions in acid/water extract from submaxillary salivary glands of rats, pigs, rabbits, mice and humans have been found [ 1,2]. Their M, values were approx.…”

Section: Introductionmentioning

confidence: 99%

Lipolytic activity of rat submaxillary salivary gland protein extracts

Paluszak¹,

Popowicz²

1981

FEBS Letters

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“…The existence of glucagon-like substances in the rat salivary gland has been reported in recent years [1][2][3][4][5][6][7]. It has been postulated that salivary gland may be one of the candidates for extrapancreatic sources of circulating glucagon, which occurs even in the pancreatectomized or eviscerated rat [1][2][3]7].…”

Section: Glucagon-degrading Activity Affinity Chromatographymentioning

confidence: 99%

125I-glucagon-degrading activity in acid-saline extracts of rat salivary gland

et al. 1984

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Summary. The antibody-binding ability of the glucagon-like substance in rat submaxillary gland acid saline extract was examined by affinity chromatography, and the biological activity studied using the isolated liver perfusion method. We found that the glucagon-like substances in acid saline extract could not be bound to anti-glucagon antibody and that the gel-filtration peak on ultrogel AcA 54 could increase neither glucose nor cyclic AMP output from isolated perfused rat liver. Furthermore, the radioactivity peak of 125I-glucagon on Bio Gel P-6 column chromatography moved from its original position and eluted in later fractions after incubation with an acid saline extract of the submaxillary gland. In consequence, there was 125I-glucagon degrading activity in the submaxillary gland, but no glucagon-related peptide. Therefore, it is suggested that the glucagon-like substance, which has been reported in acid saline extract of the rat salivary gland, may be an artifact due to tracer degrading activity.

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Salivary Gland Hyperglycemic Factor: An Extrapancreatic Source of Glucagon-Like Material

Cited by 82 publications

References 20 publications

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

Lipolytic activity of rat submaxillary salivary gland protein extracts

125I-glucagon-degrading activity in acid-saline extracts of rat salivary gland

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