Comparative effects of short-term and long-term insulin-induced hypoglycemia on glucose production in the perfused livers of weaned rats.

The liver glucose production (LGP) levels of 15-h overnight fasted weaned rats submitted to short-term insulin-induced hypoglycemia (ST-IIH) and long-term IIH (LT-IIH) were compared. Experiments to characterize ST-IIH or LT-IIH that followed an intraperitoneal (ip) injection (1.0 U/kg) of regular (ST-IIH) or insulin detemir (LT-IIH) were performed and glycemia were measured 0 (normoglycemic control), 0.5 h (ST-IIH), 4 h and 6 h (LT-IIH) later. The values of glycemia (mg/dl) were 77.8 ±l 7.2 (normoglycemic control), 26.2 ±l 6.1 (ST IIH 0.5 h), 21.2 ±l 7.6 (LT-IIH 4 h) and 35.3 ±l 14.5 (LT-IIH 6.0). The LGP levels were measured in the rats submitted to ST-IIH (0.5 h) and LT-IIH (4 h or 6 h). The rats that received ip saline were used as the normoglycemic control group (COG). The livers from the COG and IIH groups (ST-IIH or LT-IIH) were perfused in situ with infusion of L-alanine (5 mM), L-glutamine (10 mM), glutamine dipeptide (5 mM), L-lactate (2 mM) or glycerol (2 mM). The ST-IIH rats showed a higher LGP level than COG group following the L-glutamine infusion (p < 0.05), but the LGP levels that were measured following the L-lactate, L-alanine, glutamine dipeptide (5 mM), L-lactate (2 mM) or glycerol infusion remained unchanged. Moreover, if the period of IIH was expanded to 4 h following insulin injection, the LGP levels induced by L-alanine, glutamine dipeptide or glycerol infusion also increased (p < 0.05, LT-IIH vs. COG). However, the LGP from the L-lactate infusion remained unchanged until 6 h after insulin injection. In conclusion, these results suggest that the intensification of liver gluconeogenesis during ST-IIH and LT-IIH in weaned rats is not a synchronous "all or nothing" process; instead, this process integrated in a temporal manner and is specific for each gluconeogenic substrate.

Aspectos clínicos e farmacológicos do emprego do exenatide na terapêutica do diabetes mellitus tipo 2 / Clinical and pharmacological aspects of the use of exenatide for the treatment of type II diabetes mellitus

O papel do exenatide no tratamento do diabetes mellitus tipo 2 tem sido foco de intensa pesquisa. Este fármaco age como um agonista do glucagon-like peptide 1 (GLP-1), interagindo com o receptor GLP-1, estimulando a secreção de insulina pelas células ß. O exenatide também tem se mostrado altamente eficaz na redução da secreção do glucagon, esvaziamento gástrico e ingestão alimentar. Esta revisão apresenta os principais aspectos clínicos e farmacológicos do uso do exenatide em pacientes diabéticos tipo 2. Assim, concluiu-se que o exenatide representa um novo fármaco antidiabético, uma vez que estimula a secreção de insulina por um mecanismo diferente do apresentado pelas sulfoniluréias e metiglinidas (bloqueadores de canais de potássio). Além disso, enquanto todos secretagogos de insulina (incluindo os inibidores da dipepdil peptidase-4) promovem ganho de peso, o exenatide, ao contrário, favorece a perda de peso, por sua ação inibidora do apetite.

The role of exenatide in the treatment of type II Diabetes Mellitus has become the focus of intense research. This drug works as a glucagon-like peptide 1 (GLP-1) agonist as it interacts with GLP-1 receptor through the stimulation of the insulin secretion in ß cells. The exenatide also has presented to be highly effective to reduce glucagon secretion, gastric emptiness, and food intake. This review shows the major clinical and pharmacological aspects of using exenatide in type II Diabetes Mellitus patients. Thus, it was concluded that exenatide is a new antidiabetic drug; since exenatide stimulates insulin secretion by a different mechanism of sulfonylureas and metiglinides (potassium channels blockers). Moreover, in spite of the fact that all insulin secretagogues (including the dipeptidyl peptidase-4 inhibitors) in contrast exenatide promotes weight gain mediated by its inhibitory appetite action.