**1. Introduction**

Cellular survival is dependant upon the energy pathways ingrained within them. Their comprehension is imperative in understanding the role of their component enzymes in type 2 diabetes treatment and the inextricable linkage of a few of them to thiamine. The Glycolytic pathway is an ancient metabolic, cytosolic pathway that converts glucose into pyruvate under anaerobic conditions and further into lactate or ethanol. The free energy released from this forms high energy compounds ATP and NADH.Under aerobic conditions CO2 and substan‐ tially more ATP is produced [1]. The pathway of glycolysis comprises of 2 clear divisions (Fig 1). After glycolysis, further aerobic processing of glucose is conducted through the Kreb Cycle, synonymous with tricarboxylic acid or citric acid cycle (Fig 2). Intracellularly the mitochondria serve as site of citric acid cycle and oxidative phosphorylation activities.

The overall chemical reaction of the tricarboxylic acid cycle is:

<sup>+</sup> ® + 2 Acetyl-CoA + 3NAD + FAD + GDP + P + 2H O 2CO + 3NADH + FADH + GTP + 2H + HSCoA i2 2 <sup>2</sup> (1)

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the need of more expensive oral hypoglycaemic agents required by them.

*1*

*2*

**Thiamine and the Cellular Energy Cycles: A Novel Perspective on Type 2 Diabetes Treatment** 

*Pharmacology Department, Federal Postgraduate Medical Institute, Lahore, Pakistan* 

*Department of Microbiology and Molecular Genetics, University of the Punjab, Lahore, Pakistan* 

**ABSTRACT** 

None of the currently available therapeutic interventions for type 2 diabetes mellitus address the intracellular metabolism of glucose through the main energy pathways of the cell. Thiamine (vitamin B1) is a water-soluble vitamin and essential normal dietary component. When modified in the body to the pyrophosphate derivative, it acts as a coenzyme for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase & transketolase which are required for the utilization and consumption of glycolytic and hexose monophosphate pathway intermediates & form an integral part of intracellular and glucose metabolism. Thiamine deficiency decreases the activities of these enzymes, leading to imbalances in the metabolic pathways. The effects of these imbalances are more pronounced in diabetes mellitus where renal dysfunction produces mild thiamine deficiency.This indepth review presents a novel perspective on, the cellular energy cycles ,thiamine dependant enzymes,pharmacotherapeutics of type 2 diabetes especially thiamine and their impact on type 2 diabetes treatment.Thiamine, with its well established safety record, easy accessibility and affordability could be an invaluable adjunct for our type 2 diabetic population and help to improve the quality of their lives by giving them some respite from the complications of type 2 diabetes and perhaps reduce

**INTRODUCTION**

ellular survival is dependant upon the energy pathways ingrained within them. Their comprehension is imperative in understanding the role of their component enzymes in type 2 diabetes treatment and the inextricable linkage of a few of them to thiamine. This is an ancient metabolic, cytosolic pathway that converts glucose into pyruvate under anaerobic conditions (i.e. it doesn't require much oxygen) and further into lactate or ethanol. The free energy released from this forms high energy compounds ATP and NADH.Under aerobic conditions CO2 and substantially more ATP is produced

. The pathway of glycolysis comprises of 2 clear divisions (Fig1). After glycolysis,where glucose is broken down into pyruvate only releasing fractional amounts of ATP, further aerobic processing of glucose is conducted through the Kreb

**, Samreen Riaz2**

**Saadia Shahzad Alam1**

**Fig. 1 A) Phase1 (Priming Phase) of Embden Meyerhoff Pathway**  Adapted from Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu / © 1996–2011.

 **1B Phase 2 (Energy Yielding Phase) of Embden Meyerhoff Pathway Fig 1 A & B: A Schematic Pathway of glycolysis from glucose to pyruvate.and its connection to the reductive pentose pathway and citric acid cycle. Adapted from Michael W. King, Ph.D / IU School of Medicine / miking at iupui.edu / © 1996–2011. Figure 1.** (A) Phase1 (Priming Phase) of Embden Meyerhoff Pathway; (B) Phase 2 (Energy Yielding Phase) of Embden Meyerhoff Pathway; A & B: A Schematic Pathway of glycolysis from glucose to pyruvate.and its connection to the re‐ ductive pentose pathway and citric acid cycle.

**Figure 2.** Krebs cycle (www. library.thinkquest.org)
