Acarbose decreased triglyceride (TG) levels, and the areas under the curve (AUC) for insulin and glucagon more than metformin at all HbA1c levels (P < 05)

After 24 weeks treatment, metformin decreased FPG levels significantly more than acarbose for all baseline HbA1c groups (all P < 001). With the exception of FPG, PPG, and TG levels, differences between the two treatment groups observed at 24 weeks were not CONCLUSIONS: Acarbose decreased PPG and TG and spared the AUC for insulin more effectively in patients with low-to-moderate baseline HbA1c levels, whereas metformin induced greater reductions in FPG. These results may help guide selection of initial therapy based on baseline HbA1c.Oxyntomodulin analog and exendin-4 derivative lower plasma glucose in cattle.and Veterinary Medicine, Obihiro 080-8555, Japan.and Veterinary Medicine, Obihiro 080-8555, Japan.

Electronic address: The present study was undertaken with the aim of examining whether and how exendin-4 (1-3) fragment, ie, Ex-4 (1-3) fragment, contributes to the regulation of glucose. An analog of oxyntomodulin (OXM) ([Gly2, Glu3]-OXM), a glucagon analog ([Gly2, Glu3]-glucagon), and two derivatives of Ex-4 (glucandin and [Gly2, Glu3]-glucandin) were synthesized by substituting with Gly2, Glu3 at the N-terminuses of OXM and glucagon and/or by attaching Ex-4 (30-39) amide at the C-terminus of glucagon. Effects of these peptides on plasma insulin and glucose concentrations were investigated in cattle by conducting 3 in vivo experiments. In all 3 experiments, 0% BSA saline was injected as a control. In experiment 1, glucandin (amino acid sequence was glucagon [1-29]-Ex-4 [30-39] amide) and [Gly2, Glu3]-glucandin were injected at the dose rates of 5 μg/kg BW in 4-mo-old Holstein steers. Results showed that glucoregulatory effects of glucandin were similar to those of glucagon. [Gly2, Glu3]-glucandin stimulated insulin secretion at 2 to 10 min and lowered glucose concentrations at 15 to 75 min.

Experiment 2 was carried out to better understand the glucose-lowering potency of [Gly2, Glu3]-glucandin, in comparison with Ex-4 and glucagon-like peptide-1 (GLP-1), using 4-mo-old Holstein steers. [Gly2, Glu3]-glucandin was injected at dose rates of 0 μg/kg BW, 1 μg/kg BW, 3 μg/kg BW, and 6 μg/kg BW. Ex-4 and GLP-1 were injected at dose rates of 0 μg/kg BW. Results showed that the insulinotropic and glucose-lowering effects of [Gly2, Glu3]-glucandin were not as potent as for Ex-4 and GLP-1, and the minimum effective dose of [Gly2, Glu3]-glucandin to regulate plasma glucose concentrations was 3 μg/kg BW. In experiment 3, [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucagon were injected at dose rates of 5 μg/kg BW in 5-mo-old Holstein steers. Both [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucagon increased insulin concentration. [Gly2, Glu3]-OXM potently lowered plasma glucose, but [Gly2, Glu3]-glucagon did not change it.

In summary, our findings clearly demonstrate that Ex-4 (1-3) fragment contributes to the regulation of glucose. [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucandin are insulinotropic and glucose-lowering peptides. It was of interest that the substitution of the first 3 amino acids of OXM with Ex-4 (1-3) could reverse the upregulation of glucose by OXM into downregulation of glucose. In lowering glycemia, [Gly2, Glu3]-OXM seemed almost as effective as Ex-4, and [Gly2, Glu3]-glucandin was less profound than Ex-4. These findings contributed new insights into the hormonal regulation of glucose in ruminants. The action of [Gly2, Glu3]-OXM and [Gly2, Glu3]-glucandin might provide an advantage in glycemic control of insulin resistance in cattle and humans.Effect of glucagon-like peptide-1 (proglucagon 78-107amide) on hepatic glucose The newly discovered intestinal hormone, glucagon-like peptide-1 (GLP-1) (proglucagon 78-107amide), stimulates insulin secretion and inhibits glucagon secretion in man and may therefore be anticipated to influence hepatic glucose production.

To study this, we infused synthetic GLP-1 sequentially at rates of 25 and 75 pmol.kg-1.h-1 into eight healthy volunteers after an overnight fast and measured plasma concentrations of glucose, insulin, and glucagon and glucose turnover by a technique involving infusion of 3-3H-glucose. Plasma levels of GLP-1 increased by 21 +/- 3 and 75 +/- 3 pmol/L during the infusion, changes that were within physiologic limits. In a control experiment only saline was infused. During GLP-1 infusion, plasma glucose level decreased significantly (from 5 +/- 0 to 4 +/- 0 and 4 +/- 0 pmol/L at the end of the two infusion periods). Despite this, plasma insulin level increased significantly (from 20 +/- 2 to a peak value of 33 +/- 5 pmol/L during the second period), and plasma glucagon level decreased (from 9 +/- 1 to 7 +/- 1 pmol/L).

Glucose rate of appearance (Ra) decreased significantly to 75% +/- 6% of the preinfusion values during GLP-1 infusion. Glucose  glipizide 5 mg  (Rd) did not change significantly, but glucose clearance increased significantly compared with saline. All parameters of glucose turnover remained constant during saline infusion. We conclude that GLP-1 may potently control hepatic glucose production and glucose clearance through its effects on the pancreatic glucoregulatory hormones.