418
Hypoglycemic Effect
Shimura et al. (1997) investigated the hypoglycemic and hypolipidemic effect of
docosahexaenoic acid (DHA) ethyl ester in KK-Ay mice and neonatal streptozotocininduced diabetic mice, and in the normal mice. A single administration of DHA
(500 mg/kg body weight) to KK-Ay mice significantly reduced the blood glucose
levels and plasma free fatty acid levels at 10 h after oral administration when compared with the control group. DHA treated neonatal diabetic mice and normal mice,
however, showed no change in these parameters. In addition, repeated administration of DHA (100 mg/kg) to KK-Ay mice significantly suppressed the increment of
blood glucose and plasma triglyceride levels, and significantly decreased free fatty
acid at 30 days compared with control group. DHA also significantly decreased the
blood glucose at 60 and 120 min on the insulin tolerance test. It clearly shows that
DHA exhibits its hypoglycemic effects by increasing insulin sensitivity.
Similarly, Morishita et al. (2000) demonstrated the dose-related pharmacological
effects of insulin emulsion incorporating highly purified eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). Water-in-oil-in-water multiple emulsions
(insulin dose, 0, 10, 25 and 50 IU/kg) incorporating 2% DHA or EPA were administered directly into the colonic and rectal loops in situ. Serum insulin levels rose
and serum glucose levels decreased in an insulin dose-related fashion. The relationship of insulin dose and Cmax or AUC insulin was linear at the rectum, but a nonlinear relationship was observed at the colon. The trend was more predominant in
DHA. In the in vivo rectal absorption experiment using emulsions incorporating 2%
DHA, 5 IU/kg of insulin emulsion produced a rapid, transitory increase in serum
insulin levels and strong reduction of serum glucose levels. Mucosal irritation
caused by administration of emulsions incorporating 2% EPA or DHA was evaluated by a lactate dehydrogenase (LDH) release study and compared with those of
the emulsion incorporating 2% oleic or linolenic acid. The results indicate that
emulsion incorporating highly purified long-chain polyunsaturated fatty acid, especially DHA, has the potential of becoming the formulation for enteral delivery of
insulin.
Recently, Li et al. (2014) investigated the role of DHA in the prevention and
treatment of type 1 diabetes in a murine model. Streptozotocin-induced diabetic
mice were divided into control with diabetes, diabetes prevention (500 μg/kg DHA
orally for 5 days) or diabetes treatment groups (DHA solvent in DMSO into the
colon for 5 days). The groups were observed for 25 days after the administration of
DHA. Treatment with DHA greatly improved polyphagia and polydipsia, indicating improvement in diabetic conditions. Besides that DHA also showed significant
improvements in body weight. The colonic administration of DHA caused a significant increase in insulin level in the prevention and therapy groups. Histological
assessment of the pancreatic sections revealed that pancreatic cells from the DHAtreated mice were less damaged (no vacuolization and less degranulation) compared with those in the diabetic control, suggesting that there were more functional
pancreatic cells in the DHA-treated group. This may explain the higher level of
G. J. Swamy et al.
Hypoglycemic Effect
Shimura et al. (1997) investigated the hypoglycemic and hypolipidemic effect of
docosahexaenoic acid (DHA) ethyl ester in KK-Ay mice and neonatal streptozotocininduced diabetic mice, and in the normal mice. A single administration of DHA
(500 mg/kg body weight) to KK-Ay mice significantly reduced the blood glucose
levels and plasma free fatty acid levels at 10 h after oral administration when compared with the control group. DHA treated neonatal diabetic mice and normal mice,
however, showed no change in these parameters. In addition, repeated administration of DHA (100 mg/kg) to KK-Ay mice significantly suppressed the increment of
blood glucose and plasma triglyceride levels, and significantly decreased free fatty
acid at 30 days compared with control group. DHA also significantly decreased the
blood glucose at 60 and 120 min on the insulin tolerance test. It clearly shows that
DHA exhibits its hypoglycemic effects by increasing insulin sensitivity.
Similarly, Morishita et al. (2000) demonstrated the dose-related pharmacological
effects of insulin emulsion incorporating highly purified eicosapentaenoic acid
(EPA) and docosahexaenoic acid (DHA). Water-in-oil-in-water multiple emulsions
(insulin dose, 0, 10, 25 and 50 IU/kg) incorporating 2% DHA or EPA were administered directly into the colonic and rectal loops in situ. Serum insulin levels rose
and serum glucose levels decreased in an insulin dose-related fashion. The relationship of insulin dose and Cmax or AUC insulin was linear at the rectum, but a nonlinear relationship was observed at the colon. The trend was more predominant in
DHA. In the in vivo rectal absorption experiment using emulsions incorporating 2%
DHA, 5 IU/kg of insulin emulsion produced a rapid, transitory increase in serum
insulin levels and strong reduction of serum glucose levels. Mucosal irritation
caused by administration of emulsions incorporating 2% EPA or DHA was evaluated by a lactate dehydrogenase (LDH) release study and compared with those of
the emulsion incorporating 2% oleic or linolenic acid. The results indicate that
emulsion incorporating highly purified long-chain polyunsaturated fatty acid, especially DHA, has the potential of becoming the formulation for enteral delivery of
insulin.
Recently, Li et al. (2014) investigated the role of DHA in the prevention and
treatment of type 1 diabetes in a murine model. Streptozotocin-induced diabetic
mice were divided into control with diabetes, diabetes prevention (500 μg/kg DHA
orally for 5 days) or diabetes treatment groups (DHA solvent in DMSO into the
colon for 5 days). The groups were observed for 25 days after the administration of
DHA. Treatment with DHA greatly improved polyphagia and polydipsia, indicating improvement in diabetic conditions. Besides that DHA also showed significant
improvements in body weight. The colonic administration of DHA caused a significant increase in insulin level in the prevention and therapy groups. Histological
assessment of the pancreatic sections revealed that pancreatic cells from the DHAtreated mice were less damaged (no vacuolization and less degranulation) compared with those in the diabetic control, suggesting that there were more functional
pancreatic cells in the DHA-treated group. This may explain the higher level of
G. J. Swamy et al.