Anaplerosis via pyruvate carboxylase is required for the fuel-induced rise in the ATP:ADP ratio in rat pancreatic islets.

AIMS/HYPOTHESIS: The molecular mechanisms of insulin release are only partially known. Among putative factors for coupling glucose metabolism to insulin secretion, anaplerosis has lately received strong support. The anaplerotic enzyme pyruvate carboxylase is highly expressed in beta cells, and anaplerosis influences insulin secretion in beta cells. By inhibiting pyruvate carboxylase in rat islets, we aimed to clarify the hitherto unknown metabolic events underlying anaplerotic regulation of insulin secretion. METHODS: Phenylacetic acid (5 mmol/l) was used to inhibit pyruvate carboxylase in isolated rat islets, which were then assessed for insulin secretion, fuel oxidation, ATP:ADP ratio, respiration, mitochondrial membrane potential, exocytosis and ATP-sensitive K(+) channel (K(ATP)-channel) conductance. RESULTS: We found that the glucose-provoked rise in ATP:ADP ratio was suppressed by inhibition of pyruvate carboxylase. In contrast, fuel oxidation, respiration and mitochondrial membrane potential, as well as Ca(2+)-induced exocytosis and K(ATP)-channel conductance in single cells, were unaffected. Insulin secretion induced by alpha-ketoisocaproic acid was suppressed, whereas methyl-succinate-stimulated secretion remained unchanged. Perifusion of rat islets revealed that inhibition of anaplerosis decreased both the second phase of insulin secretion, during which K(ATP)-independent actions of fuel secretagogues are operational, as well as the first and K(ATP)-dependent phase. CONCLUSIONS/INTERPRETATION: Our results are consistent with the concept that anaplerosis via pyruvate carboxylase determines pyruvate cycling, which has previously been shown to correlate with glucose responsiveness in clonal beta cells. These processes, controlled by pyruvate carboxylase, seem crucial for generation of an appropriate ATP:ADP ratio, which may regulate both phases of fuel-induced insulin secretion.

Long-term development in the mandible and incisor crowding with and without an orthodontic stabilising appliance.

In children with dentoalveolar Class II malocclusion with proclined upper incisors treated with extraction of the maxillary first premolars and appliance in the upper jaw only has been reported to increase the lower arch crowding when compared with children with untreated normal occlusion. Stabilising orthodontic appliances might therefore be useful in the lower jaw. A comparison was made of Class II: 1 malocclusion with extraction in the upper arch in 35 individuals in whom a fixed orthodontic appliance was used in the upper arch only and 26 individuals with fixed appliances in both jaws. The mean age at the start of treatment was 12.9 and 12.8 years, respectively. Treatment effects and post-retention changes up to 4 to 5 years out of retention at the age of 20 to 22 years were evaluated from lateral head films and plaster casts. During treatment the orthodontic appliance in the lower arch relieved crowding. The available lower anterior space increased from -0.6 to +0.2 mm, compared, to a decrease from -0.4 to -1.3 mm in the group without mandibular appliances. After 4 to 5 years out of retention the lower arch available space had decreased in both groups, to -1.4 mm in the group where orthodontic appliances had been used in both jaws and to -2.5 mm in the group without an orthodontic appliance in the lower jaw. This difference was significant. But the subjective ranking of the amount of crowding in the lower jaw models showed no significant difference between the 2 groups at the age of 20 to 22 years.

Mandibular incisor stability after bimaxillary orthodontic treatment with premolar extraction in the upper arch.

To evaluate long-term changes in the lower incisor region, a comparison was made between children with large overjet treated with extraction of the upper first premolars and fixed appliances in both jaws and untreated children with normal occlusion. The treatment group consisted of 26 children and was studied with plaster models on 5 occasions: before treatment, at the end of active treatment, at the end of retention, after 1 year out of retention and at the last registration 4 to 5 years out of retention. The total time from the start of treatment to the last registration was 9 years and 10 months. Cephalometric registrations were made at the first and last registrations. The group of untreated children, the control group, consisted of 19 individuals. They were also studied with plaster models and lateral headfilms during a period of 10 years. The age of the treatment group and the control group at the last registration was 21.7 years and 20.4 years, respectively. At the first registration there was an available space in the lower anterior region of -0.06 mm (+/- 1.73) in the treatment group and + 0.4 mm (+/- 2.00) in the control group. At the last registration the available space for the treatment group was -1.4 mm (+/- 1.31), an extra space loss of 0.8 mm; in the control group the space loss was 1.3 mm and the available space was thus -0.9 mm. No significant difference in anterior lower jaw crowding could be seen between the treatment and control group at the last registration. Subjective ranking of the plaster models from the final registrations according to the amount of crowding in the lower anterior region showed no significant difference between the treatment and the control group.