Hypoglycemia and PDX1 Targeted Therapy

Review Article

J Endocr Disord. 2015; 2(1): 1018.

Hypoglycemia and PDX1 Targeted Therapy

Yu J¹, Liu SH¹, Sanchez R¹, Nemunaitis J² and Brunicardi FC¹*

¹Department of Surgery, University of California, USA

²Department of Surgery, Mary Crowley Cancer Research Center, USA

*Corresponding author: F Charles Brunicardi, Department of Surgery, University of California, Los Angeles, CA, USA

Received: November 07, 2015; Accepted: December 12, 2015; Published: December 15, 2015


Hypoglycemia, which refers to dangerously low glucose level in blood, is a potential life-threatening condition. The causes of different types of hypoglycemia could vary. Multiple preventive and therapeutic managements for hypoglycemia are currently under investigations. Pancreatic and Duodenal homeobox 1 (PDX1), also known as insulin promoter factor 1, is one of the most important transcriptional factors for insulin and glucose regulation in pancreatic islet beta cells. Herein, this topic will review several aspects of hypoglycemia, including the causes of hypoglycemia, PDX1 function in insulin regulation, existing hypoglycemia animal models and the potentials of PDX1 targeted therapy in treating patients with hypoglycemia.

Keywords: Hypoglycemia; PDX1; Insulinoma; Diabetes


DM: Diabetes Mellitus; PDAC: Pancreatic Ductal Adenocarcinoma; TK: Thymidine Kinase; GCV: Ganciclovir; RIP: Rat Insulin Promoter; Sstr: Somatostatin receptor


Hypoglycemia, the technical term for low blood sugar (blood glucose), is a clinical syndrome defined by abnormally low blood glucose concentrations, usually less than 3.0 mmol/L (55 mg/dl) in adults, 3.9 mmol/L (70 mg/dl) in diabetic patients or 2.2 mmol/L (40 mg/dl) in infants. The symptoms caused by hypoglycemia usually come very quickly and include a feeling of hunger, shakiness, nervousness, sweating, confusion, sleepiness, dizziness, anxiety and weakness and can lead to unconsciousness and death [1-7]. In healthy human body, the concentration of blood glucose is closely controlled and normally maintained in a narrow range, approximately between 4.0 to 6.0 mmol/L (70 to 110 mg/dl). While glucose homeostasis is very complex, for the sake of this review, glucose homeostasis is mainly regulated by two hormones insulin and glucagon (Figure 1), which are both secreted by the islets of Langerhans within thepancreas [8-13]. The regulation of blood glucose homeostasis is involved in multiple layers of regulative mechanisms [12-20]. Insulin secretion from β cells of the pancreatic islets is stimulated by high glucose concentrations, which in turn, helps transport glucose from blood into cells for proper cellular function. Secondly, extra glucose can be stored either in liver or in skeletal muscle as glycogen to prevent high glucose concentrations in bloodstream. Thirdly, when blood glucose concentration falls after a meal or during exercise, insulin secretion decreases and glucagon, produced by alpha cells in the pancreas, signals the liver to break down glycogen and release glucose back into the bloodstream. In this case, stored glycogen can be used for energy between meals and blood glucose will rise to normal levels. β cells constitutively secrete a small amount of insulin into blood stream throughout the day and night, which is also essential to maintain blood glucose concentration and prevent the liver from over secreting glucose. In general, all these protective mechanisms for regulating blood glucose hemostasis prevent the human body from hypoglycemia [21-23]. Derangements in these mechanisms can lead to hypoglycemia.