Effects of naringenin on glucose uptake in L6 skeletal muscle cells

Diabetes mellitus is a disorder of inadequate insulin action and consequent high blood glucose levels. Type 2 diabetes accounts for the majority of cases of the disease and is characterized by insulin resistance and relative insulin deficiency resulting in metabolic deregulation. It is a complex disorder to treat as its pathogenesis is not fully understood and involves a variety of defects including ~-cell failure, insulin resistance in the classic target tissues (adipose, muscle, liver), as well as defects in a-cells and kidney, brain, and gastrointestinal tissue. Present oral treatments, which aim at mimicking the effects of insulin, remain limited in their efficacy and therefore the study of the effects of novel compounds on insulin target tissues is an important area of research both for potentially finding more treatment options as well as for increasing our knowledge of metabolic regulation in health and disease. In recent years the extensively studied polyphenol, resveratrol, has been reported to have antidiabetic effects showing that it increases glucose uptake by skeletal muscle cells and prevents fatty acid-induced insulin resistance in vitro and in vivo. Naringenin, a citrus flavonoid with structural similarities to resveratrol, is reported to have antioxidan.t, antiproliferative, anticancer, and anti-inflammatory properties. Effects on glucose and lipid metabolism have also been reported including blood glucose and lipid lowering effects. However, whether naringenin has insulinlike effects is not clear. In the present study the effects of naringenin on glucose uptake in skeletal muscle cells are examined and compared with those of insulin. Naringenin treatment of L6 myotubes increased glucose uptake in a dose- and time dependent manner and independent of insulin. The effects of naringenin on glucose uptake achieved similar levels as seen with maximum insulin stimulation and its effect was additive with sub-maximal insulin treatment. Like insulin naringenin treatment did not increase glucose uptake in myoblasts. To elucidate the mechanism involved in naringenin action we looked at its effect on phosphatidylinositol 3-kinase (PI3K) and Akt, two signalling molecules that are involved in the insulin signalling cascade leading to glucose uptake. Naringenin did not stimulate basal or insulinstimulated Akt phosphorylation but inhibition of PI3K by wortmannin partially repressed the naringenin-induced glucose uptake. We also examined naringenin's effect on AMP-activated protein kinase (AMPK), a molecule that is involved in mediating glucose uptake by a variety of stimuli. Naringenin stimulated AMPK phosphorylation and this effect was not inhibited by wortmannin. To deduce the nature of the naringenin-stimulated AMPK phosphorylation and its impact on glucose uptake we examined the role of several molecules implicated in mod.ulating AMPK activity including SIRTl, LKB 1, and ca2+ Icalmodulin-dependent protein kinase kinase (CaMKK). Our results indicate that inhibition of SIRTI did not prevent the naringeninstimulated glucose uptake Of. AMPK phosphorylation; naringenin did not stimulate LKB 1 phosphorylation; and inhibition of CaMKK did not prevent naringeninstimulated glucose uptake. Inhibition of AMPK by compound C also did not prevent naringenin-stimulated glucose uptake but effectively inhibited the phosphorylation of AMPK suggesting that AMPK may not be required for the naringenin-stimulated glucose uptake.

Second Welland Canal - Book 3, Survey Map 12 - Village of Welland

Survey map of the Second Welland Canal created by the Welland Canal Company showing the canal in the Village of Welland. Identified structures and features associated with the Canal include the towing path, the old canal, the aqueduct lock, the new aqueduct, the old aqueduct, Lock Tenders House, a waste weir, culvert, covered drain, drain, dam, flume, and the canal's New Line. The surveyors' measurements and notes can be seen in red and black ink and pencil. Local area landmarks are also identified and include bridges, roads, and streets (ex. Division Street and Main Street), Chippewa Creek, Mill Pond, Mill Race, Court House and Gaol, Seeley (Seely) and Dunlop Saw Mill, Seeley (Seely) and Dunlop (Burnt) Grist Mill, Montrose Grist Mill, M. Caferty (Cafferty) City Hotel, Welland House by Wilkerson, Eli Mead Wharf Lot, A. Sherwood Wharf Lot, D. P. Myers Store, M. Cook Grist Mill, A. H. Cosby Saw Mill, Betts Lumber Yard, T. Quinn Tavern, a Carding Mill, shed, several barns, a hotel, and several structures or properties belonging to: J. P Evans, W. A. Phillips, S. Hampton, M. Silverthorne, D. McEwing, W. B. Hendershott (Hendershot), T. Burgar, J. Brookfield, A. Hendershott, Joseph Burgar, C. Demrie, M. Cafferty, J. Spencer, Mrs. Curran, John Lemon, D. Cooper, H. A. Rose, J. Bridges, A. Chapman, and R. Morewood. A structure belonging to a D. McKelly or McKully, and a store belonging to a J. Fino or Finn are also present. Properties and property owners of note are: Lots 247 and 248 of the Thorold Township, 5th Concession Lots 26 and 25 of the Crowland Township, Smith Shotwell, Eli Mead, D. P Myers, Donaldson, McFarland, Mrs. Silverthorne, Price, and Griffth. A County Court House Lot containing the Court House, Gaol and Gaol Yard is present.

Last will and testament - Peter Wright

The last will and testament of Peter Wright, dated December 18th, 1812. He was the father of Mary Wright, the first wife of Thomas Wilson (third generation). In the will, Peter states his executors as Lawrence Lemon, George Garner, and his wife Susannah Wright. There is also a transcript of the handwritten will.

Catherine Everingham land grant, 1802 [photocopy]

Catherine (Lemon) Everingham was the widow of James Everingham, a private with the first Battalion of Colo Delancys Regt. of the Jersey Volunteers. He died in the American Revolutionary War in 1796, leaving his wife and two children settled on two hundred acres of land in the Township of Willoughby. No certificate had been awarded to James Everingham for this land. Catherine subsequently petitioned the government to grant her the land that she had settled on with her family.

Plymouth Gin Advertisement

An advertisement for Plymouth Gin, it reads "Plymouth Gin. Double distilled, unsweetened; a delicious compromise between Holland and Old Tom. Unsurpassed for Cocktail, Phiz, Silver Phiz, or John Collins. Combines well with Soda and Lemon Peel. Adopted in the principal Clubs and Restaurants, with steadily increasing popularity. Recognized as invaluable medicinally. DuVivier & Co., Sole Agents. 22 Warren Street, New York. 7 Sibley Warehouses, Chicago." The image on the reverse is of a friar holding a glass surrounded by barrels and crates all labelled with company names.