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AMP-activated protein kinase (AMPK) is viewed as a fuel sensor for glucose and lipid metabolism. To better understand the physiological role of AMPK, we generated a knockout mouse model in which the AMPKalpha2 catalytic subunit gene was inactivated. AMPKalpha2(-/-) mice presented high glucose levels in the fed period and during an oral glucose challenge associated with low insulin plasma levels. However, in isolated AMPKalpha2(-/-) pancreatic islets, glucose- and L-arginine-stimulated insulin secretion were not affected. AMPKalpha2(-/-) mice have reduced insulin-stimulated whole-body glucose utilization and muscle glycogen synthesis rates assessed in vivo by the hyperinsulinemic euglycemic clamp technique. Surprisingly, both parameters were not altered in mice expressing a dominant-negative mutant of AMPK in skeletal muscle. Furthermore, glucose transport was normal in incubated isolated AMPKalpha2(-/-) muscles. These data indicate that AMPKalpha2 in tissues other than skeletal muscles regulates insulin action. Concordantly, we found an increased daily urinary catecholamine excretion in AMPKalpha2(-/-) mice, suggesting altered function of the autonomic nervous system that could explain both the impaired insulin secretion and insulin sensitivity observed in vivo. Therefore, extramuscular AMPKalpha2 catalytic subunit is important for whole-body insulin action in vivo, probably through modulation of sympathetic nervous activity.

Onychomatricoma (OM) is an uncommon benign tumor clinically characterized by a thickened yellowish nail with transverse over curvature. A pigmented variant has recently been described. Histologically, the diagnosis requires 3 prerequisites: (1) a fibroepithelial tumor consisting of 2 portions: the proximal zone (under the proximal nailfold, characterized by deep epithelial invaginations and a fibrillary and fibrocytic stroma), whereas the distal zone (corresponding to the lunula) presents with multiple digitations along its connective tissue axes; (2) a matricial tumor typified by a thick keratogenous zone; and (3) a thick nail plate, perforated by cavities. We describe a case that appears clinically identical to a pigmented OM, but with histologic malignant patterns. Because histologic features were consistent with Bowen's disease, we ruled out a malignant OM. We report a new variant of Bowen's disease presenting as OM, and this observation underlines the necessity for a histologic assessment of all forms of OM, especially those associated with a pigmented band (a sign sometimes observed in Bowen's disease).

Onychomatricoma (OM) is a tumor of the nail matrix typified histologically by multiple distal fibroepithelial projections and a thick keratogenous zone forming multiple V-shaped invaginations at the level of epithelial ridges, with the formation of a thick nail plate. In its proximal portion, the thickness of the nail looks like a spur originating from the ventral part of the nail plate. In its distal part, beyond the lunula, the nail plate is globally thickened and filled with cavities containing serous fluid. Often, however, the pathologist is not provided with the nail plate. The diagnosis then rests on the presence of a fibroepithelial tumor. In this article the histologic criteria of OM without nail plate are refined and OM is characterized immunohistochemically using three tumors fixed in liquid nitrogen and examined separately from the nail plate. On longitudinal section OM without nail plate appears as a unique pedunculated fibroepithelial tumor i.e., the multiple distal epithelial digitations arranged along a transversal plane are not seen. The feature is reminiscent of fibrokeratoma. When OM is visualized in longitudinal section, 3 main criteria differentiate OM from fibrokeratoma: the presence of epithelial-lined invaginations around optical cavities, a stroma organized in 2 layers, and the absence of horny corn. Patterns of expression of cytokeratins and integrins in OM are identical to that observed in the normal nail matrix. Involucrin finds expression from the basal layer through to the top of the epithelium, where it is more marked and where transglutaminase 1 is restricted. Merkel cells detected by CK 20 are increased in number and sometimes disposed in clusters. The fibrous component of OM is composed of 2 layers: a superficial stroma made of numerous fines fibrils of collagen IV intermingled with collagen I, and deep stroma made principally of collagen I. Antibody AE13, specific to trichocytic keratins Ha 1-4, represent a good potential marker of OM. Its V-shaped expression in epithelium ridges offers early identification of the keratogenous zone of OM, on tumors separated from their nail plates and limited to their fibroepithelial components.