Neutral Protamine Hagedorn (NPH) insulin attenuates memory impairments in diabetic rats

Abstract

Cognitive decline is a significant complication of type 1 diabetes (T1D) that substantially affects patients' quality of life. Although previous studies suggest that Neutral Protamine Hagedorn (NPH) insulin may mitigate certain effects of streptozotocin-induced type 1 diabetes (T1D_STZ), the impact of NPH on diabetes-related cognitive decline remains unclear. This study evaluated the efficacy of NPH insulin in attenuating spatial, short-term, and long-term memory deficits in T1D_STZ rats, assessing their progression at 10, 20, and 30 days following diabetes induction and treatment initiation. Sixteen adult male Wistar rats were randomly assigned into diabetic and non-diabetic groups; T1D was induced using streptozotocin (STZ). Diabetic rats received twice-daily injections of NPH insulin and underwent cognitive assessments using the Novel Object Recognition and Spatial Object Recognition tasks. NPH insulin treatment delayed the progression of memory deficits in T1D_STZ rats over the 30-day period. Although memory function was not fully restored, insulin treatment effectively delayed deficits across spatial, short-term, and long-term memory domains. However, despite treatment, T1D_STZ rats still exhibited memory impairments, highlighting the complexity of diabetes-associated cognitive decline. These findings suggest that NPH insulin offers partial neuroprotection in T1D_STZ rats, underscoring the importance of early and consistent diabetes management to preserve cognitive function. Future research should focus on refining insulin therapy strategies to enhance their effectiveness in preventing and reducing diabetes-associated cognitive impairments.

Keywords: Cognitive impairment; Diabetes complications; Insulin therapy; Memory deficits; Neuroprotection; Streptozotocin-induced diabetes.

Fig. 1

Blood glucose levels (mg/dL) before and after the training and choice phases at different time points. Blood glucose was assessed before and after the training phase, 1h30min after training, and before and after the choice phase, conducted 10 (A and B), 20 (C and D), and 30 (E and F) days post-T1D_STZ confirmation, respectively. (A, C, E) Blood glucose levels before and after the training phase, and before and after the choice phase, in Non-T1D and T1D groups. (B, D, F) Recognition index in Non-T1D and T1D groups during the corresponding time points. Statistical significance: & = Significant within-group difference (p < 0.05). + = Significant between-group difference (p < 0.05). * = Significant difference from the reference value of 0.5 (p < 0.05). # = Significant difference from day 10 (p < 0.05). The dotted line indicates the reference value of 0.5. Data are presented as means ± SD

Fig. 2

Blood glucose levels (mg/dL) before and after the sampling and choice phases at different time points. The sampling and choice phases were conducted at 10 (A, B), 20 (C, D), and 30 (E, F) days post-T1D_STZ confirmation, respectively. (A, C, E) Blood glucose levels before the sampling phase and after the choice phase in Non-T1D and T1D groups. (B, D, F) Recognition index in Non-T1D and T1D groups during the respective time points. Statistical significance: & = Significant within-group difference (p < 0.05). + = Significant between-group difference (p < 0.05). * = Significant difference from the reference value of 0.5 (p < 0.05). # = Significant difference from day 10 (p < 0.05). The dotted line indicates the reference value of 0.5. Data are presented as means ± SD