· 

SYnAbs launches unique anti-glucagon monoclonals

What is glucagon?

 

Glucagon is a small peptide of 29 amino acids that is synthesized by the alpha cells of the islets of the pancreas and by the intestinal cells. The islets also contain beta cells that produce insulin.

 

Glucagon secretion is stimulated by hypoglycemia, triglyceride consumption and increased free fatty acids.

 

What is the role of glucagon in the body?

 

Glucagon has a hormonal function opposite to that of insulin, since it causes a rise in blood sugar (hyperglycemic function). To do this, it has a function of hydrolysis of glycogen contained in the liver, which causes the release of glucose molecules into the blood. This phenomenon is called glycogenolysis.

 

The regulation of the action of insulin and glucagon makes it possible to maintain a correct blood sugar level appropriate to the effort made by the body.

 

Why test for glucagon?

 

The glucagon assay is designed for in vitro diagnostic use as an aid in the treatment of patients with disorders of carbohydrate metabolism, in particular:

  • diabetes mellitus,
  • glucagonomas: en elevation of glucagon associated with hyperglycemia or frequencies (HGPO) or decrease in glucagon levels (hypoglycemia)

The term diabetes mellitus comes from the Latin "mellitus" meaning "sweet as honey". This is type 1 diabetes, known as insulin-dependent, which is triggered by the autoimmune destruction of the so-called beta cells, or type 2 diabetes (90% of cases) via the insufficient production of insulin by these same beta cells.

 

Both type 1 and type 2 diabetes can cause marked symptoms or, on the contrary, be asymptomatic. In diabetes mellitus (type 1), the most common symptoms are excessive urine secretion (polyuria), extreme thirst (polydipsia), weight loss and a feeling of lassitude. Similar symptoms can be observed in type 2 diabetes, but they are usually less pronounced or absent altogether. For people with type 1 diabetes, daily injections of insulin are essential. For those with type 2 diabetes, it is often necessary to lower blood sugar levels.

 

The difficulty of measuring the right marker: from proglucagon to glucagon

 

Proglucagon, produced mainly in the enteroendocrine L-cells of the intestine, is a 158 amino acid protein precursor that undergoes a number of transformations to give rise to the proglucagon-derived peptide (PGDP) family.

 

The members of this family - obtained by enzymatic cleavage by the prohormone convertase (PC) enzymes PC1/3 and PC2 - include

  • intervening peptide -1 and -2 (IP1 and IP2), 3 and 18 amino acids respectively,
  • glucagon-like peptides -1 and -2 (GLP-1 and GLP-2),
  • glicentin-related pancreatic peptide (GRPP) of 30 amino acids
  • glucagon
  • oxyntomodulin (OXM), combination of glucagon and IP1
  • glicentin, a combination of GRPP and oxyntomodulin.

We know that glucagon is the marker of interest to measure for the effective diagnosis of diabetes and related cancers, but the difficulty remains to measure only glucagon without measuring its counterparts.

 

SynAbs has therefore developed a monoclonal antibody that has these characteristics.

 

SynGlucagon 1 is a mouse IgG1 that recognizes Glucagon without recognizing GLP-1 and especially without recognizing Glicentin (and consequently Oxyntomodulin and Proglucagon).

Supernatant dilution Glucagon Glicentin GLP-1 Negative control
 Pure
2,000 0,250   0,150 0,200 
x2  2,500  0,190 0,130  0,160
x4  2,600  0,160  0,110 0,110 
x8  2,600  0,120  0,100 0,080
x16  2,100  0,100  0,100 0,080 
x32  1,700  0,090  0,090 0,070 
x64  1,200  0,100  0,080 0,070 
x128  0,970  0,070  0,140  0,080 
x256  0,660  0,080  0,140  0,080 
x512 0,600 0,060 0,090 0,100
x1024  0,200  0,090  0,100 0,080 
 0  0,140  0,070  0,120  0,100