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Diabetes, a disease in which carbohydrate and lipid metabolism are regulated improperly by insulin, is a serious worldwide health issue. Insulin is secreted from pancreatic beta cells in response to elevated plasma glucose, with various factors modifying its secretion. Free fatty acids (FFAs) provide an important energy source as nutrients, and they also act as signalling molecules in various cellular processes, including insulin secretion. Although FFAs are thought to promote insulin secretion in an acute phase, this mechanism is not clearly understood. Here we show that a G-protein-coupled receptor, GPR40, which is abundantly expressed in the pancreas, functions as a receptor for long-chain FFAs. Furthermore, we show that long-chain FFAs amplify glucose-stimulated insulin secretion from pancreatic beta cells by activating GPR40. Our results indicate that GPR40 agonists and/or antagonists show potential for the development of new anti-diabetic drugs.

One of the profound changes in cellular morphology which occurs during mitosis is a massive alteration in the organization of the microfilament cytoskeleton. This change, together with other mitotic events including nuclear membrane breakdown, chromosome condensation and formation of mitotic spindles, is induced by a molecular complex called maturation promoting factor. This consists of at least two subunits, a polypeptide of relative molecular mass 45,000-62,000 (Mr 45-62K) known as cyclin, and a 34K catalytic subunit which has serine/threonine kinase activity and is known as cdc2 kinase. Non-muscle caldesmon, an 83K actin- and calmodulin-binding protein, is dissociated from microfilaments during mitosis, apparently as a consequence of mitosis-specific phosphorylation. We now report that cdc2 kinase phosphorylates caldesmon in vitro principally at the same sites as those phosphorylated in vivo during mitosis, and that phosphorylation reduces the binding affinity of caldesmon for both actin and calmodulin. Because caldesmon inhibits actomyosin ATPase, our results suggest that cdc2 kinase directly causes microfilament reorganization during mitosis.

At mitosis in eukaryotic cells there are profound changes of shape and structure whose causes are almost entirely obscure. What is known is that there are changes in the organization of microfilaments, including the disassembly of microfilament bundles during prophases and the accompanying rounding-up of cultured cells; the formation of transient contractile rings during cytokinesis; and, subsequently, the reassembly of microfilament bundles and the respreading of the two daughter cells. As an initial step towards the biochemical understanding of these events, in which the disassembly and reassembly of microfilaments appear to play an important part, we searched for alterations of the molecular constitution of microfilaments during mitosis. We found that non-muscle caldesmon, a protein with a relative molecular mass (Mr) of 83,000 (83K) which binds to actin and calmodulin, is dissociated from microfilaments during mitosis, apparently as a consequence of phosphorylation. This process may contribute to the changes of shape and structure of cells in mitosis, as caldesmon inhibits actomyosin ATPase.

A suitable motility model reconstituted from non-muscle contractile proteins should offer a powerful tool for analysing the molecular events in cell motility. Actomyosin thread has been thought to be such a model. As far as non-muscle motile systems are concerned, however, only a very limited number of experiments have been done in this direction. No direct measurement of the tension produced by non-muscular actomyosin thread has been reported in spite of its importance for quantitative studies. We now report that a segment of actomyosin thread of Physarum polycephalum can generate a considerable amount of tension, which is a function of the micromolar concentration of ATP. The maximum isometric tension was a high as 10 g cm-2 at 10 microM ATP.