Ⅱ型糖尿病患者中医辨证分型与空腹血胰高糖素含量的关系

通过对３２例ＮＩＤＤＭ患者空腹血胰高糖素及胰岛素含量的测定，我们发现ＮＩＤＤＭ患考空腹血胰高糖素含量常明显增高（Ｐ＜０．０１），而胰岛素含量则无明显增高（Ｐ＞０．０５），支持“糖尿病的发生是由于胰高糖素分泌过多与胰岛素分泌相对不足”的观点。进一步分析ＮＩＤＤＭ患者中医辩证分型与空腹血胰高糖素含量的关系，则见气阴两虚型及阴阳两虚型胰高糖素含量均明显高于对照组（Ｐ＜０．０１），其中尤以阴阳两虚型升高最明显、与气阴两虚型相比亦有显著性差异（Ｐ＜０．０５），从而为ＮＩＤＤＭ患者的中医辨证提供了新的客观依据。

胰高糖素和胰高糖素瘤综合征

胰高糖素(glucagon)由胰岛A细胞所分泌,并刺激B细胞及D细胞使之分别分泌胰岛素及生长激素释放抑制因子。在正常情况下,胰高糖素与胰岛素之间保持一定的动态平衡以维持体内血糖水平。胰岛各种分泌细胞之间通过联结复合体相互联结,此种构造有助于协调彼此间的激素分泌。

Is Glucagon-like peptide-1, an agent treating diabetes, a new hope for Alzheimer's disease?

Glucagon-like peptide- 1 （GLP- 1） has been endorsed as a promising and attractive agent in the treatment of type 2 diabetes mellitus （T2DM）. Both Alzheimer＇s disease （AD） and T2DM share some common pathophysiologic hallmarks, such as amyloid β （Aβ）, phosphoralation of tau protein, and glycogen synthase kinase-3. GLP-1 possesses neurotropic properties and can reduce amyloid protein levels in the brain. Based on extensive studies during the past decades, the understanding on AD leads us to believe that the primary targets in AD are the Aβ and tau protein. Combine these findings, GLP- 1 is probably a promising agent in the therapy of AD. This review was focused on the biochemistry and physiology of GLP- 1, communities between T2DM and AD, new progresses of GLP - 1 in treating T2MD and improving some pathologic hanmarks of AD.

Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation

Short bowel syndrome （SBS） refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn＇s disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable. Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 （GLP-2） is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is atrophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor （GLP-2R） remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.

EFFECTS OF GLUCAGON ON ISLET β CELL FUNCTION IN PATIENTS WITH DIABETES MELLITUS

Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.

Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degen- eration in Raw 264.7 cells involving the AMPK/SREBP1 pathway

Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.

Uncoupling protein 2 regulates glucagon-like peptide-1 secretion in L-cells

AIM:To investigate whether uncoupling protein 2(UCP2) affects oleic acid-induced secretion of glucagonlike peptide-1(GLP-1) in L-cells.METHODS:mRNA and protein expression of UCP2 were analyzed in human NCI-H716 cells,which serve as a model for enteroendocrine L-cells,by quantitative reverse transcription-polymerase chain reaction and Western blotting before and after treatment with oleic acid.Localization of UCP2 and GLP-1 in NCI-H716 cells was assessed by immunofluorescence labeling.NCI-H716 cells were transiently transfected with a small interfering RNA(siRNA) that targets UCP2(siUCP2) or with a nonspecific siRNA using Lipofectamine 2000.The concentrations of bioactive GLP-1 in the medium were measured by enzyme linked immunosorbent assay.RESULTS:Both GLP-1 and UCP2 granules were expressed mainly in the cytoplasm of NCI-H716 cells.NCI-H716 cells that secreted GLP-1 also expressed UCP2.Time-course experiments revealed that release of GLP-1 from NCI-H716 cells into the medium reached a maximum at 120 min and remained stable until at least 180 min after treatment with oleic acid(the level of GLP-1 increased about 2.3-fold as compared with the level of GLP-1 in the control cells,P < 0.05).In an experiment to determine dose dependence,stimulation of NCI-H716 cells with ≤ 8 mmol oleic acid led to a concentration-dependent release of GLP-1 into the medium;10 mmol oleic acid diminished the release of GLP-1.Furthermore,GLP-1 secretion induced by oleic acid from NCI-H716 cells that were transfected with siUCP2 decreased to 41.8%,as compared with NCI-H716 cells that were transfected with a non-specific siRNA(P < 0.01).CONCLUSION:UCP2 affected GLP-1 secretion induced by oleic acid.UCP2 plays an important role in L-cell secretion that is induced by free fatty acids.

Olive oil consumption and non-alcoholic fatty liver disease

The clinical implications of non-alcoholic fatty liver diseases(NAFLD)derive from their potential to progress to fibrosis and cirrhosis.Inappropriate dietary fat intake,excessive intake of soft drinks,insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride(TG)accumulation.An olive oil-rich diet decreases accumulation of TGs in the liver,improves postprandial TGs,glucose and glucagonlike peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver.The principal mechanisms include:decreased nuclear factor-kappaB activation,decreased lowdensity lipoprotein oxidation,and improved insulin resistance by reduced production of inflammatory cytokines(tumor necrosis factor,interleukin-6)and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1.The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids,mainly from olive oil.In this review,we describe the dietary sources of the monounsaturated fatty acids,the composition of olive oil,dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis,clinical and experimental studies that assess the relationship between olive oil and NAFLD,and the mechanism by which olive oil ameliorates fatty liver,and we discuss future perspectives.

Pathologic pancreatic endocrine cell hyperplasia

Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known.β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy,which is commonly caused by mutations in the islet ATP-sensitive potassium channel,and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors.An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge. Based on morphological evidence,the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium.Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia,elevated islet hormone levels,and pancreatic neuroendocrine tumors.Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

Immuolocalization of nestin in pancreatic tissue of mice at different ages

AIM： To localize nestin positive cells （NPC） in pancreatic tissue of mice of different ages. METHODS： Paraffin sections of 6-8 um of fixed pancreatic samples were mounted on poly-L-lysine coated slides and used for Immunolocalization using appropriate primary antibodies （Nestin, Insulin, Glucagon）, followed by addition of a fluorescently labeled secondary antibody. The antigen-antibody localization was captured using a confocal microscope （Leica SP 5 series）. RESULTS： In 3-6 d pups, the NPC were localized towards the periphery of the endocrine portion, as evident from immunolocalization of insulin and glucagon, while NPC were absent in the acinar portion. At 2 wk, NPC were localized in both the exocrine and endocrine portions. Interestingly, in 4-wk-old mice NPC were seen only in the endocrine portion, towards the periphery, and were colocalised with the glucagon positive cells. In the pancreas of 8- wk-old mice, the NPC were predominantly localized in the central region of the islet clusters, where immunostaining for insulin was at a maximum. CONCLUSION： We report for the first time the immunolocalization of NPC in the pancreas of mice of different ages （3 d to 8 wk） with reference to insulin and glucagon positive cells. The heterogeneous localization of the NPC observed may be of functional and developmental significance and suggest（s） that mice pancreatic tissue can be a potential source of progenitor cells. NPC from the pancreas can be isolated, proliferated and programmed to differentiate into insulin secreting cells under the appropriate microenvironment.

Effect of Acupuncture on Plasmic Levels of Insulin,Glucagon and Hypercoagulability in NIDDM Complicated by Acute Cerebral Infarction

Twenty-one cases of acute cerebral infarction secondary to NIDDM were treated with acupuncture and conventional therapy, and compared with 16 cases treated with conventional therapy alone. The results showed that acupuncture was more effective in reducing insulin and glucagon levels (P

EFFECT OF CHRONIC ACE INHIBITIONONGLUCOSE TOLERANCE AND INSULIN SENSITIVITY IN HYPERTENSIVE TYPE 2 DIABETIC PATIENTS

We studied 14 moderately overweight Typo 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period , and again after 3 months of antihypertensive treatment with the angiotensin-converting enzyme (ACF) inhibitor captopril. Glucose tolerance was tested with a 75g oral glucose load (OGTT) and insulin sensitivity was measured by the insulin suppression test (IST) while dietary and drug treatment of the hyperglycemia was maintained constant. In the whole group. mean blood pressure (MBP) fell progressively over 3months from a baseline value of 123± 3 mmHg (1 mmHg= 0. 133 kpa) to a final value of 115± 2 mmHg(P<0. 005). After treatment, fasting plasma glucose, insulin, free fatty acid (FFA). potassium, and glycosylated hemoglobin concentrations were unchanged from baseline. There were no significant differences in glucose tolerance and insulin sensitivity between pre- and post-trearment values. Neither endogenous (oral glucose) nor exogenous (IST) insulin caused any change in plasma potassium concentration. This resistance to the hypokalemic action of insulin was not affected by captopril.

Hypercalcemia Appeared in a Patient with Glucagonoma Treated with Octreotide Acetate Long-acting Release

PABCREATIC neuroendocrine tumours are uncommon neoplasms of the pancreas.They may cause a clinical syndrome due to hormone overproduction.Glucagonoma is a rare kind of pancreatic tumors. Here we report a case of glucagonoma. Hypercalcemia occurred when the patient underwent octreotide acetate long-acting release.

Removal of Dominant Adrenal Lateralized by Glucagon-Stimulated Adrenal Venous Sampling Alleviates Hypertension in Bilateral Pheochromocytoma

In bilateral pbeochromocytoma, localization of the dominant adrenal is challenging but highly important since the removal of dominant side can markedly improve cardiovascular outcomes. To demonstrate the usefulness of glucagon-stimulated BAVS （bilateral adrenal venous sampling） in determining the dominant adrenal to be removed, the authors reviewed records of patients who underwent BAVS with glucagon stimulation from 1997-2010. Nineteen out of 44 patients were diagnosed with bilateral pheochromocytoma. Mean age at diagnosis was 33 ± 14 years. Duration of hypertension was 5 ± 6 years with highest systolic BP （blood pressure） of 186 ±30 mmHg and diastolic BP of 113 ±18 mmHg. Headache （68%） is the most common symptom followed by paroxysmal hypertension （58%）. Majority were taking 〉 3 anti-hypertensive drugs. On glucagon-stimulated BAVS, 63% had right adrenal dominance. Three patients, who were hypertensive for 1, 6 and 12 years, underwent removal of the dominant adrenal. On follow-up （mean period = 36 months）, there was marked improvement in BP control [pre-op vs. post-op： （systolic） 160-240 mmHg vs. 120-150 mmHg; （diastolic） 90-110 mmHg vs. 70-90 mmHg] and reduction in number of anti-hypertensive medications （from 3-5 to 2 classes of drugs）. BAVS with glucagon stimulation is a valuable tool in the identification of the dominant adrenal to be removed in patients with bilateral pheochromocytoma to alleviate chronic hypertension.

Hyperinsulinemic hypoglycemia due to diffuse nesidioblastosis in adults:A case report

Persistent hyperinsulinemic hypoglycemia is caused most commonly by an insulinoma in adults or by nesidioblastosis in neonates. In adults, nesidioblastosis is a rare disorder characterized by diffuse or disseminated proliferation of islet cells. We recently encountered a case of nesidioblastosis in an adult. A 71-year-old man was admitted due to intermittent general weakness, abdominal pain, and mild dyspnea. The patient underwent a subtotal gastrectomy for a gastric adenocarcinoma two years ago. After 5 d of admission, the patient showed symptoms of cold sweating, chilling, and hypotension 30 min after eating. Thereafter, he frequently showed similar symptoms accounting for hypoglycemia regardless of food consumption. Laboratory findings revealed a low fasting blood glucose level （25 mg/dL）, and a high insulin level （47 μIU/mL）. Selective intra-arterial calcium stimulation with hepatic venous sampling （ASVS） was performed to localize a mass and revealed an increased insulin level about fourfold that of the normal fasting level at 60 s in the splenic artery, which suggested the presence of an insulinoma in the tail of pancreas. A distal pancreatectomy was performed. Neither intraoperative exploration nor a frozen biopsy specimen detected any mass-forming lesion. On the histological examination, many of the islets were enlarged and irregularly shaped in all specimens, the arrangement of which was a Iobulated islet pattern. Cytologically, a considerable subpopulation of endocrine cells showed enlarged and hyperchromatic nuclei. By immunohistochemistry, the cells were identified as p-cells. These clinical, radiological, microscopic and immuno-histochemical findings are consistent with diffuse nesidioblastosis in adults.

Advancements in glucagon-like peptide-1 receptor agonist therapy for type 2 diabetes

Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglycemic effects,and metabolic advantages.Their primary mechanisms of action encompass promoting insulin release,inhibiting glucagon secretion,bolstering pancreatic islet cell function,curbing appetite,and slowing gastric emptying.This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs.Notably,these agents have demonstrated marked improvements in glycemic control,significant weight reduction,and substantial cardiovascular and renal protection.Nonetheless,certain adverse effects of GLP-1RAs,such as pancreatitis and intestinal obstruction,have been reported,warranting vigilant monitoring by healthcare professionals.In sum,GLP-1RAs hold significant promise in the management of type 2 diabetes,offering notable cardiovascular and renal advantages.

Effects of acupoint thread-embedding therapy on serum apelin and GLP-1 in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen

Objective:To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1(GLP-1)in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.Methods:Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method,with 33 cases in each group.Patients in the control group were treated with exenatide and metformin,while patients in the observation group were treated with additional acupoint thread-embedding.After 12-week treatment,the obesity-related indicators,including body mass index(BMI),waist circumference and body fat rate,the glycometabolism indicators,including fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin,and the lipid metabolism indicators,including total cholesterol(TC),triglyceride(TG)and low-density lipoprotein cholesterol(LDL-C),as well as serum apelin and GLP-1 levels were observed in patients of the two groups.Results:After treatment,the BMI,waist circumference and body fat rate of patients in the two groups were all reduced(all P<0.05),and were lower in the observation group than in the control group(all P<0.05);the fasting blood glucose,2 h postprandial blood glucose and glycosylated hemoglobin levels of patients in both groups were all decreased(all P<0.05),and were significantly lower in the observation group than in the control group(all P<0.05);the TC level was decreased(P<0.05),while the TG and LDL-C levels did not change significantly in the control group(both P>0.05);the TC,TG and LDL-C levels were all significantly reduced in the observation group(all P<0.05),lower than those in the control group(all P<0.05);the serum apelin level was decreased(P<0.05)and the serum GLP-1 level was increased(P<0.05)in the observation group,statistically different from those in the control group(both P<0.05).Conclusion:Combined with the conventional medication,acupoint thread-embedding therapy can significantly improve the obesity-related indicators,glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen.This may be achieved by regulating the serum apelin and GLP-1 levels.

Electroacupuncture for functional dyspepsia and the influence on serum Ghrelin, CGRP and GLP-1 levels

Objective： To observe the clinical efficacy of electroacupuncture for functional dyspepsia（FD）, and explore the corresponding mechanism.Methods： Sixty-four FD patients were randomly divided into electroacupuncture group and western medicine group, with 32 cases in each group. In electroacupuncture group, electroacupuncture at Zusanli（足三里ST 36）,Sanyinjiao（三阴交SP 6）,Gongsun（公孙SP 4） and Neiguan（内关PC 6） was performed for once a day, and the needles were retained for 30 min. In western medicine group, oral administration of mosapride citrate dispersible tablets in a dosage of 5 mg/time was carried out for 3 times a day. Treatment was conducted for 30 consecutive days in both groups. The scores of Leeds dyspepsia questionnaire（LDQ） and functional digestive disorder quality of life（FDDQL） of patients in both groups were recorded before and after treatment. Serum Ghrelin, CGRP and GLP-1 levels of patients were tested before and after treatment respectively, and the clinical efficacy of patients in both groups was evaluated after treatment.Results： In western medicine group, LDQ score after treatment was lower than that before treatment（P 0.05）, FDDQL score after treatment was higher than that before treatment, while the differences were not statistically significant（P0.05）. LDQ score in electroacupuncture group after treatment was lower than that before treatment（P0.05）, and also lower than that in western medicine group at the same time point（P 0.05）. FDDQL score in electroacupuncture group after treatment was higher than that before treatment（P0.05）, and also higher than that in western medicine group at the same time point（P0.05）. In western medicine group, Ghrelin level after treatment was higher than that before treatment（P 0.05）, CGRP level reduced, and the differences were not statistically significant（P 0.05）. GLP-1 level after treatment was also higher than that before treatment（P0.05）. In electroacupuncture group,Ghrelin level after treatment was higher than that before treatment, CGRP level reduced, and GLP-1 level after treatment was also higher than that before treatment（both P 0.05）. According to the comparison of values of each index between electroacupuncture group and western medicine group after treatment,the differences were all statistically significant（all P 0.05）. The total effective rate in electroacupuncture group was 90.63%（29/32） which was higher than that in western medicine group 68.75%（22/32）, and the differences were statistically significant（P0.05）.Conclusion： Electroacupuncture at ST 36, SP 6, SP 4 and PC 6 can effectively improve the clinical symptoms of FD patients, and the mechanism might be related with the increase of serum Ghrelin and GLP-1 levels and the decrease of serum CGRP level.

Modeling and qualitative analysis of diabetes therapies with state feedback control

For the therapies of diabetes mellitus, a uovel mathematical model with two state impulses： impulsive injection of insulin and impulsive injection of glucagon, is proposed. To avoid hypoglycemia and hyperglycemia, the injections of insulin and glucagon are determined by closely monitoring the plasma glucose level of the patients. By using differential equation geometry theory, the existence of periodic solution and the attrac- tion region of the system have been obtained, which ensures that injections in such an automated way can keep the blood glucose concentration under control. The simula- tion results verify that the better insulin injection strategy in closed-loop control is a larger dose but longer interval rather than a smaller dose but shorter interval. Besides, our numerical analysis reveals that medicine studies and practice that slow down the insulin degradation are helpful for the plasma glucose control. Our findings can provide significant guidance in both design of artificial pancreas and clinical treatment.