GLP-1(7-37)

When blood glucose is elevated, the product binds to GLP‑1R on pancreatic β‑cell surfaces, activating the intracellular cAMP/PKA pathway. This leads to phosphorylation of the sulfonylurea receptor SUR1 and the inward‑rectifying potassium channel Kir6.2, causing potassium channel closure, plasma membrane depolarization, and opening of voltage‑dependent calcium channels. Calcium influx ultimately promotes exocytosis of insulin granules. This effect is strictly glucose‑dependent and weak at normoglycemia, mechanistically preventing hypoglycemia-a key advantage over conventional antidiabetic agents.

The product activates the cAMP/PKA pathway in pancreatic α‑cells, inhibiting glucagon synthesis and secretion, reducing hepatic glycogenolysis and gluconeogenesis, and lowering hepatic glucose output, thereby further assisting glycemic control. This forms a dual glycemic‑lowering loop of "insulin promotion plus glucagon suppression". Studies indicate this pathway reduces glucagon secretion by 50%–65%, significantly ameliorating disordered hepatic glucose metabolism.

The product acts on GLP‑1R in gastrointestinal smooth muscle and enteric nerve terminals, slowing gastric emptying and intestinal peristalsis, reducing the rate of glucose absorption from food, and preventing sharp postprandial blood glucose spikes. Signals are transmitted via the vagus nerve to the hypothalamic arcuate nucleus, activating satiety‑associated POMC neurons and inhibiting hunger‑promoting AgRP neurons, reducing food intake by 18%–30% and enhancing satiety.

Chronic exposure promotes pancreatic β‑cell proliferation, inhibits β‑cell apoptosis, increases β‑cell mass by approximately 25%, and improves islet functional reserve. It also ameliorates insulin resistance, reduces body weight, and optimizes the lipid profile (lowering triglycerides and low‑density lipoprotein cholesterol), comprehensively improving core indicators of metabolic syndrome.

The product reduces cardiovascular risk by improving vascular endothelial function, inhibiting inflammatory responses, regulating cardiomyocyte metabolism, and attenuating myocardial ischemia‑reperfusion injury. It promotes nitric oxide production, inhibits atherosclerotic plaque formation, and helps reduce the incidence of adverse outcomes such as myocardial infarction and heart failure.

GLP‑1R is widely distributed in the brain. The product improves cognitive and motor functions in animal models of Alzheimer's disease and Parkinson's disease through anti‑inflammatory, antioxidant, anti‑apoptotic mechanisms and enhanced synaptic plasticity. Its effects involve reducing Aβ amyloid deposition, inhibiting tau hyperphosphorylation, and increasing brain‑derived neurotrophic factor (BDNF) expression, providing a new direction for intervention in neurodegenerative diseases.

The N‑terminal functional domain of it is the key motif recognized and bound by GLP‑1R. It specifically interacts with the receptor's extracellular domain, inducing a conformational shift of GLP‑1R from a resting state to an active conformation. GLP‑1R is a class B G protein‑coupled receptor widely expressed in tissues including the pancreatic islets, gastrointestinal tract, central nervous system, and cardiovascular system, forming the basis for multi‑tissue regulation by it.

Following receptor conformational change, the intracellular coupled Gαs subunit is activated. Dissociated Gαs binds to adenylate cyclase (AC), markedly enhancing its catalytic activity and accelerating the conversion of ATP to cyclic adenosine monophosphate (cAMP), leading to a rapid increase in intracellular cAMP concentration and initiation of downstream signaling cascades.

Elevated cAMP activates protein kinase A (PKA), which modulates ion channels and secretion‑related proteins in pancreatic β‑cells via phosphorylation. In β‑cells, PKA phosphorylates L‑type calcium channels to promote Ca²⁺ influx and trigger insulin exocytosis; it also phosphorylates the CREB transcription factor, upregulating insulin gene (INS) and PDX‑1 expression to enhance insulin synthesis and storage. In α‑cells, PKA inhibits cAMP signaling and Ca²⁺ influx, reducing glucagon secretion and achieving bidirectional glycemic control.

It also independently regulates cellular functions through the exchange protein directly activated by cAMP (Epac) pathway. As a cAMP effector independent of PKA, Epac modulates β‑cell proliferation and apoptosis, gastrointestinal motility, and central synaptic plasticity. In pancreatic β‑cells, the Epac pathway synergistically enhances insulin secretion and stabilizes β‑cell function. In the central nervous system, it participates in appetite suppression and cognitive regulation, expanding the physiological regulatory network of it.

It is stable in acidic environments and resistant to peptide bond hydrolysis within pH 2.0–6.0, but readily degrades under alkaline conditions (pH > 8.0); thus, buffer pH must be controlled during experimental preparation. It is also susceptible to proteolytic degradation, particularly by dipeptidyl peptidase‑4 (DPP‑4), which cleaves the N‑terminal His‑Ala peptide bond and abolishes bioactivity. Protease contamination must be avoided in experimental settings.

7-37-Glucagon-likepeptide is freely soluble in water, with optimal solubility in pH 5.0–7.0 buffers (phosphate‑buffered saline, Tris‑HCl buffer). It is partially soluble in polar organic solvents such as methanol and ethanol, and nearly insoluble in non‑polar solvents including n‑hexane and chloroform. Aqueous buffers are preferred for solution preparation to avoid non‑polar solvents.

Solid Form

Store in sealed packaging at −20°C or −80°C in the dark, avoiding repeated removal from low‑temperature environments (temperature fluctuations may cause moisture absorption and degradation). When unopened and properly stored, the shelf life is typically 12–24 months (varies by supplier; some formulations remain stable for up to 3 years). Short‑term room‑temperature transport before experiments does not compromise stability.

Solution Form

Prepare solutions immediately before use to avoid prolonged storage. For short‑term preservation, aliquot into small volumes (to prevent repeated freeze‑thaw cycles, which cause polypeptide aggregation and degradation), add 0.02% sodium azide or a DPP‑4 inhibitor, and store at −80°C for no longer than 1 month. Solutions stored at 4°C are only stable for 1–2 days; strict aseptic technique is required to prevent microbial contamination that may affect experimental results.

7-37-Glucagon-likepeptide is the developmental basis for blockbuster GLP‑1 receptor agonists including semaglutide, liraglutide, and dulaglutide. These drugs resist DPP‑4 degradation via structural modifications (e.g., fatty acid side‑chain conjugation), extending their half‑lives to several days or one week while retaining the glucose‑dependent hypoglycemic properties of native 7-37-Glucagon-likepeptide. Clinically, they significantly reduce HbA1c and postprandial glucose in patients with type 2 diabetes, improve β‑cell function, and carry an extremely low risk of hypoglycemia, becoming first‑line options for type 2 diabetes treatment.

Based on its physiological effects of appetite suppression, delayed gastric emptying, and increased energy expenditure, GLP‑1 (7‑37)‑related targets are central to obesity treatment. Current research further explores synergistic effects with other metabolic targets, focusing on dual‑ or triple‑agonists targeting GIP and glucagon receptors (e.g., tirzepatide). By integrating multiple metabolic pathways, these agents significantly enhance weight loss and improve metabolic markers such as lipids and waist circumference, offering new strategies for obesity and metabolic syndrome.

Animal studies confirm that it improves cognitive and motor functions in models of Alzheimer's and Parkinson's diseases. Neuroprotective mechanisms include inhibition of neuroinflammation, reduction of oxidative stress, suppression of neuronal apoptosis, enhancement of synaptic plasticity, and decreased Aβ deposition and tau phosphorylation. Related research is currently in the preclinical stage, with multiple clinical trials underway to evaluate the therapeutic potential of GLP‑1 receptor agonists for neurodegenerative diseases, potentially opening non‑traditional intervention pathways.

The cardiovascular protective effects of it have become a research focus in metabolic cardiovascular disease. Preclinical studies show it improves endothelial function, inhibits cardiomyocyte apoptosis, attenuates myocardial ischemia‑reperfusion injury, and regulates blood pressure and lipids. Multiple cardiovascular outcome trials confirm that GLP‑1 receptor agonists reduce cardiovascular events (myocardial infarction, stroke) in type 2 diabetes patients. Ongoing research is dissecting the molecular mechanisms of its direct cardiovascular actions, defining its value in integrated management of cardiovascular comorbidities, and driving label expansion.