The endocrine secretion of human insulin and growth hormone by exocrine glands of the gastrointestinal tract

Goldfine, Ira D.; German, Michael S.; Tseng, Hsien-Chen; Wang, Juemin; Bolaffi, Janice L.; Chen, Je-Wei; Olson, David C.; Rothman, Stephen

doi:10.1038/nbt1297-1378

Cited by 91 publications

(68 citation statements)

References 17 publications

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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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“…There are also strong HLA associations. 29 and exocrine pancreas. 29 The most productive results have been achieved by using vector carrying furin-modified insulin.…”

Section: Discussionmentioning

confidence: 99%

“…Acinar cells are capable of exporting protein into the bloodstream, as well as the ductal lumen, and blood borne proteins enter the portal circulation. 29,31,32 High level gene transfer in the rat and mouse pancreas have been shown using adenoviral vectors. Intra-ductal and direct intra-pancreatic injections are efficient ways to deliver adenoviral vector into the mouse pancreas.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adenoviral vector-mediated insulin gene transfer in the mouse pancreas corrects streptozotocin-induced hyperglycemia

Shifrin

Auricchio

et al. 2001

Gene Ther

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“…Preproinsulin biosynthesis has been achieved in a variety of endocrine cells like K-cells (48) or cells from pituary (49)(50)(51), exocrine pancreas (52), and submandibular glands (42), as well as in nonendocrine cells like muscle cells (53,54), and fibroblasts (55). However, in some of the endocrine cell lines (e.g.…”

Section: Engineering Of a Surrogate β-Cellmentioning

confidence: 99%