Sweet Temptation, bitter Truth: Diabetes in the Research Spotlight | Biomol Blog | Resources

Written by Josephine Frey

The increasing number of people suffering from diabetes poses major challenges for the healthcare system, particularly due to the serious secondary diseases [1]. “Overweight and obesity are among the most important avoidable and preventable medical problems of our time,” says Professor Dr. med. Hans Hauner from the Department of Nutritional Medicine at the TU Munich [2]. Around 80% of all new diagnoses of type 2 diabetes are set by doctors in people who are overweight [3].

But why is weight so closely linked to the risk of developing diabetes? Being overweight is often associated with increased glucose or fat levels in the blood. As a result, the insulin-producing cells of the pancreas are overstressed, which can lead to exhaustion of the organ and ultimately to type 2 diabetes [4]. Conversely, studies have shown that weight loss can help to control blood glucose levels and may even reverse the development of type 2 diabetes [5].

Despite ongoing research, many aspects of this complex metabolic disease are still not well understood. At Biomol, we equip scientists with high-quality products from our specialized manufacturers around diabetes and obesity research to enable the discovery of new treatments. In this article, you will learn more about the underlying mechanisms of diabetes and its two types and get an overview of current research trends as well as the different types of products from our manufacturers and their applications.

These topics await you:

1) How Sugar Metabolism works

2) Diabetes and its Origins

3) Weight loss Injections on the Road to Success: the Go-to GLP-1R Agonist Semaglutide

4) Two (or even three) Birds with one Stone: the Receptor Agonists Tirzepatide and Retatrutide

5) Why more Research is still needed and how the Biomolecule Activin can help

6) Understanding Diabetes Targets better - with Reporter Cell Lines and Assays

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How Sugar Metabolism works

When we eat something, the body absorbs the glucose - commonly called sugar - contained in the food into the bloodstream. To maintain the balance, the pancreas constantly “measures” the blood sugar level (Fig. 1): If it’s too high, the pancreas reacts by releasing the peptide hormone insulin from the insulin-producing beta cells of the islets of Langerhans. This ensures that the somatic cells absorb the sugar from the blood and the liver can store the glucose [6]. If the amount of glucose in the blood is too low, the peptide hormone glucagon is released from the Alpha cells of the pancreas, which in turn leads to the release of the sugar stored in the liver and causes the blood sugar level to rise [7].

Diabetes_Figure_1_final

Figure 1: Regulation of blood glucose levels by the pancreas. Insulin lowers blood glucose levels and glucagon increases our blood glucose levels [8].

Our brain, red blood cells and renal medulla are dependent on a constant supply of glucose as an energy source. The sugar can either be transported for direct consumption, e.g. to the brain via glucose transporter 1 (GLUT1), or for storage in muscle or liver cells via GLUT4. If the blood glucose level is out of balance for a long time and there is a permanently increased amount of glucose in the blood, this is known as hyperglycaemia, which promotes chronic diseases such as renal insufficiency or diabetes mellitus [9]. On the other hand, a blood sugar level that is permanently too low can lead to hypoglycemia and result in permanent brain damage [10].

Diabetes and its Origins

Diabetes mellitus is a metabolic disease that is based on insulin resistance or deficiency and is characterized by chronically high blood sugar levels. It is also associated with an increased risk of serious secondary diseases [5]. These include cardiovascular diseases such as heart attacks or strokes, which makes diabetes research all the more important [11].

A distinction is made between two types of diabetes (Fig. 2): Type 1 diabetes is an autoimmune disease in which the immune system mistakenly attacks the insulin-producing cells of the pancreas and destroys them. As a result, the body can no longer produce enough insulin [12]. Type 2 diabetes is slightly different: Here, there is both a reduced release of insulin and a reduced reaction of the body's cells to insulin [13].

Diabetes_Figure_2_new

Figure 2: Pathogenesis of type 1 and type 2 diabetes. A healthy pancreas reacts to an increase in blood glucose levels with rapid insulin secretion by the beta cells, which leads to glucose uptake in various tissues. Type 1 diabetes is caused by a lack of insulin due to destruction of the beta cells, which prevents glucose uptake from the blood. Type 2 diabetes is caused by reduced insulin effect or production and also leads to rising blood glucose levels (image created with biorender.com).

In addition to type 2 diabetes, severe obesity can also lead to other chronic diseases such as heart disease or some types of cancer [14]. Obesity research is therefore essential and requires long-term investment to develop effective treatments and prevention strategies for this complex disease.

Weight loss Injections on the Road to Success: the Go-to GLP-1R Agonist Semaglutide

You have probably come across terms such as Ozempic or Wegovy at one time or another. These are so-called “weight loss injections” that contain the active ingredient Semaglutide and have become increasingly popular among antidiabetics in recent years.

Semaglutide is an antidiabetic drug that belongs to the group of so-called incretin mimetics. As a GLP-1 receptor agonist, it mimics the body's own hormone GLP-1 (glucagon-like peptide-1) and selectively binds to the GLP-1 receptor, thereby stimulating the secretion of insulin and lowering blood glucose levels [15]. Semaglutide also has an appetite-reducing effect. Due to its effect as a brain messenger and the slowing down of gastric emptying, it also leads to weight loss [16].

Sounds great at first, but unfortunately there is a big problem: Semaglutide is advertised on social media as a risk-free miracle cure for weight loss, which has led to a shortage in the supply of this active ingredient for type 2 diabetics [17]. As a result, diabetics often had to visit several pharmacies to obtain their prescribed medication. Andreas Klinge, a diabetologist and board member of the German Medical Association's Drug Commission, stated that he had never experienced such hype surrounding a drug in twenty years of medical practice [18].

In addition to the shortage, the active ingredient itself also poses a problem. “Weight loss injections” with Semaglutide can cause side effects such as nausea, vomiting and, in the long term, a yo-yo effect. One possible alternative is medication that acts simultaneously on several receptors as so-called multifunctional agonists. These could not only offer improved blood sugar control, but also more efficient weight reduction with fewer side effects.

Two (or even three) Birds with one Stone: the Receptor Agonists Tirzepatide and Retatrutide

If a primary GLP-1 receptor agonist such as Semaglutide is not enough, there are other rays of hope in diabetes research. One of these is the dual GIP/GLP-1 receptor agonist Tirzepatide (Fig. 3). Tirzepatide combines the effect of two incretins - GLP-1 and the glucose-dependent insulinotropic polypeptide (GIP) - and is therefore also known as “Twincretin” [20].

Since the end of 2023, this drug, which was originally intended as a pure antidiabetic, can now also be used for weight loss in adults with obesity [21]. It acts as a highly selective agonist at receptors of the incretins GLP-1 and GIP, thereby increasing the amount of insulin released in a glucose-dependent manner. Due to its dual agonistic effect, Tirzepatide proved to be even more effective in its weight-reducing effect than Semaglutide.

Diabetes_Figure_3

Figure 3: Principles of action of poly-agonists at GLP-1, GIP and glucagon receptors [19].

The triple agonist of the GLP-1R, GIPR and glucagon receptor (GCGR) is even more effective (Fig. 3): Retatrutide effectively activates the GLP-1R signaling pathway to stimulate glucose-dependent inuslin secretion through activity at the GIPR or GLP-1R. Due to the additional effect on the glucagon receptor, Retatrutide appears to lead to even more effective weight loss than Semaglutide or Tirzepatide [22]. According to current studies, the side effects of multiple agonists largely correspond to the already known side effects of GLP-1 agonists such as Semaglutide [23].

So, if you are now curious about all the receptor agonists involved in diabetes research, you can choose from a comprehensive range of both new and tried-and-tested products from our selected manufacturers:

***GLP-1, GIP & GCG Receptor Agonists from AdipoGen Life Sciences and Cayman Chemical***
Product Number	Product Name	Description
AG-CP3-0034	Liraglutide	Long-acting acylated GLP-1 receptor Agonist
AG-CP3-0040	Semaglutide	Longer-acting alternative GLP-1 receptor agonist to Liraglutide
AG-CP3-0032	Semaglutide . AcOH	Semaglutide salt form
AG-CP3-0043	Tirzepatide	Novel dual GIP and GLP-1 receptor agonist
AG-CP3-0044	Retatrutide . sodium salt	Novel triple agonist peptide of the GCG, GIP and GLP-1 receptors
Cay40231	Semaglutide	A GLP-1R agonist
Cay29969	Semaglutide (acetate)	A GLP-1R agonist
Cay40170	Semaglutide (sodium salt)	A GLP-1R agonist
Cay40746	Semaglutide Side Chain	A synthetic intermediate
Cay39739	Lixisenatide (acetate)	A GLP-1R agonist
Cay24727	Liraglutide	A potent agonist of the GLP-1 receptor
Cay40298	[Gly8,36,Glu22]-GLP-1 (7-37)	A GLP-1 derivative and fragment of dulaglutide
Cay35847	Exendin-4 (5-39) amide	An antagonist of the GLP-1 receptor
Cay11096	Exendin-4 (48-86) amide	A GLP-1R agonist
Cay39748	Tirzepatide (sodium salt)	A dual GLP-1R and GIP receptor agonist
Cay39747	Retatrutide (sodium salt)	A GCGR, GLP-1R, and GIP receptor agonist

Discover more biomarkers for your research on diabetes, obesity, insulin resistance, inflammation and much more:

***Top Products from AdipoGen Life Sciences***
Produktnummer	Produktname	Größe
AG-45A-0001YEK-KI01	Adiponectin (human) ELISA Kit	96 wells \| 2 x 96 wells
AG-45A-0004YEK-KI01	Adiponectin (mouse) ELISA Kit	96 wells \| 2 x 96 wells
AG-45A-0006YEK-KI01	Nampt (Visfatin/PBEF) (human) ELISA Kit	96 wells \| 2 x 96 wells
AG-45A-0017YEK-KI01	Vaspin (human) ELISA Kit	96 wells \| 2 x 96 wells
AG-40A-0018-C050	Nampt (Visfatin/PBEF) (human, rec.) (His)	50 µg
AG-20A-0034	Anti-Nampt (Visfatin/PBEF), clone OMNI379	50 µg \| 100 µg
AG-45B-0010-KI01	Asprosin (human) ELISA Kit	96 wells
AG-45B-0032-KI01	Isthmin-1 (human) ELISA Kit	96 wells

Why more Research is still needed and how the Biomolecule Activin can help

Various studies have already demonstrated new functions of certain biomolecules in the regulation of body weight, appetite control, glucose homeostasis and metabolic diseases [24]. One of these biomolecules is the proteo- or protein hormone activin. Doesn't mean anything to you? Don't panic, we'll introduce you to the wondrous world of this biomolecule and its influence on the metabolic diseases type 2 diabetes and obesity.

Activin is produced in the granulosa cells of the ovaries and the Sertoli cells of the testicles. It stimulates the release of the follicle-stimulating hormone, FSH for short, from the pituitary gland and thus contributes to the regulation of the female menstrual cycle [25]. But that's not all, because activin can do even more! It also influences glucose metabolism by increasing insulin sensitivity through increased expression of glucose transporters such as GLUT4 and thus improving glucose uptake. This makes activin and the associated signaling pathway a highly interesting field of research!

Understanding Diabetes Targets better - with Reporter Cell Lines and Assays

Last but not least, we would like to introduce you to another ace up our sleeve: the luciferase reporter cell lines from BPS Bioscience. The cells are suitable for use in high-throughput systems to screen for inhibitors or agonists. The product range includes among others cells that express the glucagon receptor GCGR, the thyroid hormone receptor beta (TRβ), GLP-1R or GIPR. By using these highly specific cell lines, researchers can obtain precise data on the effect of various active substances in relevant metabolic processes, which is crucial for the development of new therapeutic approaches.

Diabetes_Figure_4

Figure 4: Measurement of receptor activity by luciferase production (image created with biorender.com).

Use the precise reporter cell lines and assays from our manufacturer BPS Bioscience to make your research more efficient and targeted! Inducible reporter assays, especially luciferase reporters, which are linked to the activation of specific signaling pathways for example by the GIP receptor, provide a reliable measurement of the inhibitory or activating effect of substances on diabetes-associated cell signaling pathways (Fig. 4). Discover TGFß/activin A-sensitive reporter cells for efficient measurement of receptor activation by activin A. Pin addition, perform high-throughput screening of receptor agonists or antagonists and reliably determine corresponding EC50 or IC50 values!

***Reporter Cell Lines and Inhibitor Screening Assays from BPS Bioscience***
Product Number	Product Name	Description
BPS-78176	GLP-1R/CRE (Luc) Reporter - HEK293 Recombinant Cell Line	Constitutive expression of human GLP-1R
BPS-82187	GCGR/CRE Luciferase Reporter HEK293 Cell Line	Constitutive expression of human GCGR
BPS-78589	GIPR/CRE Luciferase Reporter HEK293 Cell Line	Constitutive expression of human GIPR
BPS-82175	TRβ-GAL4 Luciferase Reporter HEK293 Cell Line	Constitutive expression of human thyroid receptor beta ligand binding domain
BPS-60653	TGFβ/Activin A-Responsive Luciferase Reporter HEK293 Cell Line	TGF signaling pathway activity monitoring
BPS-82531	Activin A: Activin RIIB[Biotinylated] Inhibitor Screening Assay Kit	Measure the binding between Activin A and Activin RIIB (receptor IIB)
BPS-102121	Activin Blocker	Use as control to block the binding between Activin A and ACVRIIB
BPS-79605	ALK2 (ACVR1) Kinase Assay Kit	Measure the serine/threonine kinase activity of ACVR1
BPS-78819	TGFβR1 (ALK5) Kinase Assay Kit	Measure the serine/threonine kinase activity of TGFβR1 (ALK5)