Avaliação do efeito da administração de nanocápsulas de insulina no epitélio intestinal e no tecido adiposo de ratos alimentados com dieta hipercalórica

Abstract

Obesity and type 2 diabetes mellitus are major public health problems closely linked to metabolic and cardiovascular complications. Oral insulin remains challenging due to degradation in the gastrointestinal tract, and polymeric nanocapsules have been proposed to enhance intestinal delivery.To evaluate the effect of orally administered insulin‐loaded nanocapsules on small-intestinal histomorphometry and adipose tissue in Wistar rats fed a conventional diet or a high-fat diet (HFD).Male Wistar rats (n=90) received daily oral treatment for 37 days with insulin-loaded nanocapsules (0.2 or 0.4 mL) or control formulations, under conventional diet or HFD. Body weight was monitored; fasting glycemia and ketone bodies were determined at the end of treatment. Duodenum, jejunum, and ileum were processed for histology and histomorphometric measurements (villus height and crypt depth). Retroperitoneal, omental, and epididymal fat pads were weighed.As expected, HFD increased body weight and abdominal adiposity compared with the conventional diet. Oral insulin nanocapsules did not change fasting glycemia or ketone bodies relative to the corresponding dietary controls. In contrast, intestinal histomorphometry revealed significant diet × treatment interactions, with insulin nanocapsules—particularly under HFD—associated with increased villus height and deeper crypts in small-intestinal segments, most notably in the jejunum. These findings are consistent with a local trophic effect on the intestinal mucosa. Effects on adipose depots were limited and group-specific, without a consistent reduction in fat mass. Thirty-seven days of oral insulin-loaded nanocapsules promoted morphological changes compatible with enhanced intestinal trophism, without detectable systemic effects on fasting glycemia. The data support a primarily local intestinal action in this timeframe; longer interventions and additional biomarkers are warranted to clarify systemic metabolic impact.