Insulin replacement prevents the acquisition but not the expression of morphine-induced conditioned place preference in streptozotocin-induced diabetic rats

Abstract Insulin receptors have distributed in all brain regions, including the nucleus Accumbens (NAc), and where is implicated in the reward properties of drugs. It is well known that insulin signaling can regulate dopamine release. Therefore, in the present study, we tried to examine the effect of insulin replacement on the acquisition and expression of morphine-induced conditioned place preference (CPP) in diabetic rats. Forty-eight male Wistar rats were divided into two non-diabetic (Naïve) and diabetic groups rendered by a single injection of streptozotocin (STZ). These groups separately received insulin (10U/kg) or saline (1 ml/kg) one hour prior to morphine administration (5mg/kg;s.c.) during conditioning days (acquisition phase) or post-conditioning day (expression phase) in the CPP paradigm. In this paradigm, conditioning score (CS) and locomotion activity were recorded by Ethovision. The STZ-induced diabetic rats displayed higher CS compared to naïve rats (P<0.05). This effect was abolished in all diabetic rats that received insulin during conditioning days but not the expression phase. This study has provided evidence that insulin plays a modulatory role in morphine-induced CPP, and insulin replacement during the acquisition phase could reduce the rewarding properties of morphine in diabetes conditions through a possible modulating effect on dopamine release in the NAc region

Giving insulin is not a guessing game: Insulin replacement therapy in type 2 diabetes mellitus

@#<p style="text-align: justify;" data-mce-style="text-align: justify;">In 2021, 537 million adults were living with diabetes. Being a progressive disease, there would eventually be failure of oral hypoglycemic agents (OHA) to maintain good glycemic control and a majority will require insulin. However, optimal glycemic control has not been satisfactory in a significant proportion of patients who were on insulin therapy. Patient factors (eg, awareness, compliance, socioeconomic) have been identified but physician-related factors are as important. These include incorrect choice and inappropriate combination of insulin therapy which could be corrected by making the treatment physiologic. The purpose of this article is to improve management decisions in type 2 diabetes by reviewing its pathophysiology and identifying the optimum insulin regimen that could mimic such. Since eventual beta cell failure is central to its pathophysiology, it is but reasonable to replace insulin by mimicking its physiologic secretion. Hence, the term Insulin Replacement Therapy (IRT) should be utilized. This could be provided by the combination of premix insulin (ie, NPH + regular insulin) and rapid-acting insulin which has been reported to provide an initial 17.5% HbA1c reduction and even 18% reduction on 5-year follow-up providing sustainable control. A stepwise approach is an effective tool for insulin intensification. Hypoglycemia in insulin therapy could be prevented with an appropriate dietary regimen through automatic snacking.</p>