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Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 5 uppsatser.

Thesis (M.S.)--University of Wisconsin--Madison, 1969. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Cold exposure impacts intestinal remodelling and metabolism. Signaling by glucagon-like peptide 1 (GLP-1), GLP-2 and glucose-dependent insulinotropic polypeptide (GIP) are tightly linked to nutrient intake and absorption. However, these peptide hormones' necessity to mediate gut adaptation and metabolic alternations during cold exposure has been incompletely explored. We hypothesize that GLP-1, GIP, and GLP-2 are released in proportion to required energy needs during cold exposure to enable efficient nutrient absorption and gut adaptation and subsequently impact nutrient handling. We evaluated morphological changes in the intestinal in wildtype, Glp1r-/-Glp2r-/- and Glp1r-/-Gipr-/- mice exposed to chronic cold or thermoneutral conditions for four weeks. Food intake and gut hormone secretion were significantly increased in all mice housed at 4-6 ̊C compared to those housed at thermoneutrality. Concomitantly, we observed increased remodeling measured by crypt to villus height (increased villi length) and intestinal circumference (increased circumference) in cold-exposed wildtype and Glp1r-/-Gipr-/- mice housed. In contrast, intestinal morphology in Glp1r-/-Glp2r-/- mice was unchanged in response to cold. Associated with these morphometric changes, we observed significant increases in fasting concentrations of GLP-1. These data suggest that GLP-1 and GLP-2 are key signaling molecules secreted from the gut in response to chronic cold exposure to enable intestinal remodeling.

Digitized by Kansas Correctional Industries

The aims of this thesis were to establish a suitable model system for the study of glucose and nutrient regulation of insulin secretion and biosynthesis. This would serve as a basis for investigating the GLP-1 effects on pancreatic b-cell biology. This thesis shows that two b-cell model systems, namely MIN6 and INS-1 cells, respond to increasing concentrations of glucose, by increasing insulin secretion and cell proliferation in a physiological manner. The MIN6 cell line also responds to other cellular nutrients, L-arginine and L-leucine in a manner similar to primary islet cells. The MIN6 cells however, fail to consistently increase insulin secretion in response to GLP-1, a known potentiator of insulin secretion in b-cells, despite the presence of the GLP-1 receptor. Incubation of GLP-1 with INS-1 cells, increases insulin secretion in a glucose-dependent manner, and causes a small increase in cell proliferation. GLP-1 is also known to increase cAMP levels within the cell and interact with cAMP response elements (CRE) via activation protein kinase A (PKA). Using a luciferase reporter gene construct containing 4 copies of the CRE, glucose, GLP-1 and forskolin failed to increase luciferase activity in MIN6 cells, suggesting that a defect in cAMP signalling may explain the inconsistent effect of GLP-1 in MIN6 cells. A stimulatory effect of GLP-1 and forskolin was observed in the INS-1 cells. Using both a rat insulin I and human insulin gene promoter construct, a stimulatory effect of GLP-1 on insulin gene transcription was observed in INS-1 cells. An insight into the signalling pathways involved in GLP-1 stimulation of the rat insulin I gene was gained through the use of protein kinase inhibitors, which inhibit signalling of known signal transduction cascades. It was found that an inhibitor of protein kinase A (H-89) was effective in blocking the increase in insulin promoter activity induced by GLP-1 using the rat insulin I promoter construct. Interestingly, the p38/SAPK2 inhibitor, SB203580, further increased the GLP-1 stimulation of rat insulin I promoter activity, indicating that this pathway usually invokes an inhibitory effect on insulin promoter activity.

Thesis (M. S. in Molecular Physiology and Biophysics)--Vanderbilt University, Aug. 2008. / Title from title screen. Includes bibliographical references.

Th. 3e cycle--Pharm., physiol--Paris 5, 1982. N°: 36.

No description available.