Rai Uddipak, Senapati Dhirodatta, Arora Mandeep Kumar
School of Pharmaceutical and Population Health Informatics, DIT University, 248009, Dehradun, Uttarakhand India.
Diabetol Int. 2022 Nov 17;14(2):134-144. doi: 10.1007/s13340-022-00607-9. eCollection 2023 Apr.
Diabetes is a major health problem worldwide. It is a chronic metabolic disorder that produces overt hyperglycemic condition that occurs either when the pancreas does not produce enough insulin due to excessive destruction of pancreatic β-cells (type 1 diabetes) or due to development of insulin resistance (type 2 diabetes). An autoimmune condition known as type 1 diabetes (T1D) results in the targeted immune death of β-cells that produce insulin. The only available treatment for T1D at the moment is the lifelong use of insulin. Multiple islet autoantibody positivity is used to diagnose T1D. There are four standard autoantibodies observed whose presence shows the development of T1D: antibodies against insulin, glutamic acid decarboxylase (GAD65), zinc T8 transporter (ZnT8), and tyrosine phosphatase-like protein (ICA512). In type 2 diabetes (T2D), an inflammatory response precipitates as a consequence of the immune response to high blood glucose level along with the presence of inflammation mediators produced by macrophages and adipocytes in fat tissue. The slow and chronic inflammatory condition of adipose tissue produces insulin resistance leading to increased stress on pancreatic β-cells to produce more insulin to compensate for the insulin resistance. Thus, this stress condition exacerbates the apoptosis of β-cells leading to insufficient production of insulin, resulting in hyperglycemia which signifies late stage T2D. Therefore, the therapeutic utilization of immunosuppressive agents may be a better alternative over the use of insulin and oral hypoglycemic agents for the treatment of T1D and T2D, respectively. This review enlightens the immune intervention for the prevention and amelioration of T1D and T2D in humans with main focus on the antigen-specific immune suppressive therapy.
糖尿病是全球主要的健康问题。它是一种慢性代谢紊乱疾病，会导致明显的高血糖状态，这种情况要么是由于胰腺β细胞过度破坏导致胰腺分泌胰岛素不足（1型糖尿病），要么是由于胰岛素抵抗的发展（2型糖尿病）引起。一种名为1型糖尿病（T1D）的自身免疫性疾病会导致产生胰岛素的β细胞发生靶向性免疫死亡。目前T1D唯一可用的治疗方法是终身使用胰岛素。多种胰岛自身抗体阳性用于诊断T1D。观察到有四种标准自身抗体，它们的存在表明T1D的发展：抗胰岛素抗体、谷氨酸脱羧酶（GAD65）抗体、锌转运体8（ZnT8）抗体和酪氨酸磷酸酶样蛋白（ICA512）抗体。在2型糖尿病（T2D）中，对高血糖水平的免疫反应以及脂肪组织中巨噬细胞和脂肪细胞产生的炎症介质的存在会引发炎症反应。脂肪组织的缓慢慢性炎症状态会产生胰岛素抵抗，导致胰腺β细胞承受更大压力以产生更多胰岛素来补偿胰岛素抵抗。因此，这种应激状态会加剧β细胞的凋亡，导致胰岛素分泌不足，从而引发高血糖，这意味着T2D进入晚期。因此，对于T1D和T2D的治疗，分别使用免疫抑制剂进行治疗可能比使用胰岛素和口服降糖药更好。这篇综述阐述了针对人类T1D和T2D的预防和改善的免疫干预措施，主要关注抗原特异性免疫抑制疗法。
