Published online Sep 15, 2022. doi: 10.4239/wjd.v13.i9.752
Peer-review started: March 11, 2022
First decision: April 25, 2022
Revised: May 13, 2022
Accepted: August 22, 2022
Article in press: August 22, 2022
Published online: September 15, 2022
Oral administration of benzylamine (Bza) exerts antihyperglycemic effects in obese and diabetic rodent models. This effect has been proposed to depend on the insulin-like action of Bza in adipose cells. The amine oxidation catalyzed by amine oxidases abundantly present in adipocytes generates hydrogen peroxide, which activates glucose transport.
To extrapolate the potential antihyperglycemic properties of Bza found in obese and diabetic models to the treatment of insulin-deficient type 1 diabetic states. Bza administration might facilitate glucose utilization to increase lipogenic and adipogenic activities in the adipose tissue and thereby improve glucose disposal even in the absence of insulin.
To evaluate the impact of Bza supplementation on hyperglycemia, polydipsia and hyperphagia in type 1 diabetic mouse, and to demonstrate that Bza metabolism by adipose tissue supports these antidiabetic effects.
Bza solution (5 g/L, Bza-drinking) replaced drinking water in streptozotocin (STZ)-induced, insulin-deficient diabetic mice. Similar comparison between control and Bza-drinking groups was performed in normoglycemic mice. Nonfasting blood glucose, water and food intake were periodically recorded in the four groups. Adiposity was determined at the end of a 24-d treatment. Glucose transport in freshly isolated adipocytes was assessed ex vivo by determining the uptake of the nonmetabolizable radiolabeled 2-deoxyglucose.
Chronic Bza intake did not normalize hyperglycemia in STZ diabetic mice, despite it alleviating excessive water and food consumption. Bza intake had no effect on the limited body weight of the STZ diabetic mice and could not restore their dramatically reduced adipose tissue mass. In normoglycemic mice, the Bza-drinking group did not show altered body weight, or food or water consumption. However, when directly given in vitro to adipocytes isolated from nondiabetic mice, Bza was efficient in activating glucose uptake in both control and Bza-drinking groups.
The capacity of Bza supplementation to reduce hyperglycemia, previously reported in obese and diabetic rodents, was not detectable in the emaciated and insulin-deficient STZ diabetic mice. However, the capacity of Bza to activate glucose transport in adipocytes was confirmed in nonobese, nondiabetic mice. It is likely that the adipose tissue atrophy induced by STZ challenge hampered the lipogenic and adipogenic action of Bza in this severe model of lipoatrophic, insulin-deficient diabetes.
The current findings and their interpretations considerably limit the field of applications of oral Bza since this molecule did not work as an antidiabetic agent in rodents with reduced adiposity, as it is the case in type 1 STZ diabetic and lipoatrophic mice. Nevertheless, since SSAO substrates exhibit a direct action on glucose handling by fat cells, they still have potential interest for therapeutic use to combat other diabetic states.