Model of Streptozotocin-nicotinamide Induced Type 2 Diabetes: a Comparative Review

Abstract

: The aim of the present study was to review the streptozotocin-nicotinamide (STZ-NA) diabetes model. Type 2 diabetes is more prevalent (90-95%) in adults than type 1. Experimentally-induced diabetes models may be established by chemicals, viral agents, insulin antibodies, surgery, etc. The most advisable and prompt method to induce diabetes is using chemicals, and STZ and alloxan are widely used chemicals. STZ has proven to be a better diabetogenic agent than alloxan because alloxan has many drawbacks, as it induces only type 1 diabetes, has a high mortality rate in rats, and causes ketosis in animals. Moreover, it has lesser selectivity towards β-cells, and the diabetes-induced is reversible. STZ can be used to induce both type 1 and type 2 diabetes. It is noted that the genotoxic behavior of STZ in animals is accomplished through a reduction of nicotinamide adenine dinucleotide (NAD+) in pancreatic β-cells via the GLUT2 (Glucose transporter 2), which can cause cellular damage by DNA (Deoxyribonucleic acid) strand breaks that lead to cell death. NA is a biochemical precursor of NAD+, and it is a poly-ADP-ribose-polymerase-1 (PARP-1) inhibitor. NAD+ is an important redox reaction co-enzyme for the production of adenosine triphosphate (ATP) and many other metabolic pathways. Extreme DNA damage contributes to the over-activation of PARP-1, loss of cellular resources, and necrotic cells death. Some studies have expressed that NA can protect pancreatic β-cells against the severe cytotoxicity of STZ. The review concluded that the STZ-NA model is dependent on the competency of NA to attain partial protection against the β-cytotoxic essence of STZ to induce type-2 diabetes.

Palm Oil Derived Tocotrienol-Rich Fraction Attenuates Vascular Dementia in Type 2 Diabetic Rats

“…T2DM was induced by administering a single dose of STZ and NA. Numerous studies have shown that the STZ and NA diabetes model is valuable in investigations of various aspects of diabetes since STZ is known to damage pancreatic B-cells, while NA is given to rats to partially protect insulin-secreting cells against STZ [ 38 , 39 ]. In the present study, T2DM was confirmed in rats by the increased levels of fasting blood glucose, the condition called hyperglycemia [ 40 ], and it was constant in T2DM rats throughout the study.…”

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation

“…66 Owing to the toxic damage caused by Alloxan to the liver and kidney and the high rate of ketosis, ALX has now been gradually replaced by STZ. 67…”

“…Alloxan also triggers the necrosis of pancreatic islet l3 cells by producing reactive oxygen clusters, leading to decreased insulin secretion, elevated blood glucose and ketosis 66 . Owing to the toxic damage caused by Alloxan to the liver and kidney and the high rate of ketosis, ALX has now been gradually replaced by STZ 67 …”

Therapy Combining Glucagon-Like Peptide-1 Receptor Agonist with Sodium-Glucose Cotransporter 2 Inhibitor Suppresses Atherosclerosis in Diabetic ApoE-Deficient Mice

“…The amount of food intake and body weight were measured once a week. We created a mouse model of type 2 diabetes in which pancreatic β-cells were damaged but not completely destroyed, by pretreating with nicotinamide (NA) followed by streptozotocin (STZ), a β-cell toxin [27]. Therefore, we administered NA 120 mg/kg and STZ 100 mg/kg to 8-week-old mice by peritoneal injection twice every other day.…”