No abstract

Metformin lowers blood glucose by reducing hepatic glucose output and improving insulin sensitivity without requiring an increase in circulating insulin concentration. We hypothesized that metformin could be used adjunctively with insulin to improve glycemic control in type 1 diabetes mellitus (DM). We conducted a 6-month open-label pilot study in 10 adolescents and young adults with type 1 DM, 19.1 +/- 3.4 years, 4 males, 6 females, and body mass index 26.3 +/- 3.1 kg/m2. Patients started metformin at a dose of 250 mg b.i.d.; the dose was increased until blood glucose was within an optimal target range or a maximum of 2,500 mg/d was reached. Insulin dose was reduced as needed to prevent hypoglycemia. Seven patients had an average decrease in HbA(1c) of 11% from pretreatment. These responders had no change in insulin dose, BMI or lipid levels during the study. Three patients had no improvement of HbA(1c) on therapy. We conclude that some patients with type 1 DM will have improved glycemic control on adjunctive metformin therapy. Evaluation of the long-term benefit and safety of adjunctive therapy in patients with type 1 DM is warranted.

The basement membrane protein laminin-1 is a potent stimulator of neurite outgrowth for a variety of neuronal cell types. Previous studies have identified neurite outgrowth activity in several distinct regions of the laminin-1 molecule. In this study, 545 overlapping 12- to 14-mer synthetic peptides, corresponding to most of the amino acid sequence of the alpha1, beta1, and gamma1 chains of laminin-1, were screened for cell attachment and neurite outgrowth activity using primary cultures of mouse cerebellar granule neurons and two neuronal cell lines. We identified 48 peptides derived from novel regions of the laminin-1 molecule that were positive for neural cell adhesion activity. Only the cerebellar cells were found to have true neurite outgrowth activity with certain of the peptides, whereas some peptides induced short spike-like process with the cell lines. Although 23 of these peptides were active on all 3 cell types screened, 25 others showed cell-type specificity in their activity. These studies show that (1) there are multiple and distinct sites on laminin-1 for cell adhesion and neurite-like outgrowth and (2) that there are neural cell-type-specific active domains. The multiple active sites found explains, in part, the potent activity of laminin-1 on neurite outgrowth.