Metformin-induced glucagon-like peptide-1 secretion contributes to the actions of metformin in type 2 diabetes

Background: Metformin reduces plasma glucose and has been shown to increase glucagon-like peptide 1 (GLP-1) secretion. Whether this is a direct action of metformin on GLP-1 release, and whether some of the glucose-lowering effect of metformin occurs due to GLP-1 release, is unknown. The current study investigated metformin-induced GLP-1 secretion and its contribution to the overall glucose-lowering effect of metformin and underlying mechanisms in patients with type 2 diabetes. Methods: Twelve patients with type 2 diabetes were included in this placebo-controlled, double-blinded study. On 4 separate days, the patients received metformin (1,500 mg) or placebo suspended in a liquid meal, with subsequent i.v. infusion of the GLP-1 receptor antagonist exendin9-39 (Ex9-39) or saline. During 240 minutes, blood was sampled. The direct effect of metformin on GLP-1 secretion was tested ex vivo in human ileal and colonic tissue with and without dorsomorphin-induced inhibiting of the AMPK activity. Results: Metformin increased postprandial GLP-1 secretion compared with placebo (P = 0.014), and the postprandial glucose excursions were significantly smaller after metformin + saline compared with metformin + Ex9-39 (P = 0.004). Ex vivo metformin acutely increased GLP-1 secretion (colonic tissue, P < 0.01; ileal tissue, P < 0.05), but the effect was abolished by inhibition of AMPK activity. Conclusions: Metformin has a direct and AMPK-dependent effect on GLP-1-secreting L cells and increases postprandial GLP-1 secretion, which seems to contribute to metformin's glucose-lowering effect and mode of action.Emilie Bahne, Emily W.L. Sun, Richard L. Young, Morten Hansen, David P. Sonne, Jakob S. Hansen, Ulrich Rohde, Alice P. Liou, Margaret L. Jackson, Dayan de Fontgalland, Philippa Rabbitt, Paul Hollington, Luigi Sposato, Steven Due, David A. Wattchow, Jens F. Rehfeld, Jens J. Holst, Damien J. Keating, Tina Vilsbøll, and Filip K. Kno

The Effects of Business Taxes on Output and Location of the Firm under Uncertainty

[[abstract]]In this article, a triangular production-location model is used to show that when output price is random, the imposition of business taxes (including lump-sum tax, profit tax, output tax, and input tax) can have significant effects on the optimal location and output of a firm attempting to maximize a von Neumann-Morgenstern utility function of profits. In addition, using the concept of differential incidence, the authors also made a comparison of the magnitudes of the impacts of these taxes on the output and location of the firm and indicates that the effects of these taxes differ according to the tax structure.[[journaltype]]國

MANUFACTURING FIRMS' VIEWS OF GOVERNMENT ACTIVITY AND COMMITMENT TO SITE: IMPLICATIONS FOR BUSINESS RETENTION POLICY

Relationships between a variety of firm characteristics and perceptions of government are investigated. Then views about government are considered in connection with firms' commitment to their present location. One finding that is well supported is that taxes and regulations (at least for this sample and within this region) are a source of considerable dissatisfaction. Satisfaction with government services does not come near "offsetting" the displeasure with taxes and regulations. Larger firms are more likely to have unfavorable perceptions of government constraints, but more likely to have favorable views about government services. There is no evidence from this data that high tech firms differ significantly from other firms in their views about government. In regards to implications for business retention, the findings support the notion that state governments seeking to market their state to businesses located elsewhere might turn a greater proportion of attention to businesses currently residing in the state. Copyright 1987 by The Policy Studies Organization.