Insulin and IGF-I analogs: novel approaches to improved insulin pharmacokinetics

Slieker, Lawrence J.; Brooke, G. S.; Chance, Ronald E.; DiMarchi, Richard D.; Fan, Ludi; Hoffman, J. A.; Howey, Daniel C.; Long, H B; Mayer, John P.; Shaw, W. N.; Shields, James E.; Sundell, Karen

doi:10.1007/978-94-010-9066-7_2

Cited by 7 publications

(9 citation statements)

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“…This effect is probably achieved through inhibition of arteriolar vasodilatation, as suggested by the prevention of meal-induced RVR decrease. These findings provide support to our working hypothesis that lispro may inhibit IGF-1-dependent renal vasodilation (26,27), possibly through antagonism for the IGF-1 receptors located on mesangial cell surface. This effect is specific for lispro, since previous studies found that human insulin may have opposite effects on renal hemodynamics, thereby resulting in a trend to increase GFR and RPF (39) and to synergize the vasodilator effects of blood glucose (40).…”

Section: Metabolic Studiessupporting

confidence: 82%

“…In this regard, it has been recently found that a recombinant insulin analog (insulin lispro), because of the transposition of proline and lysine at position 28 and 29 in the COOH-terminal of the b ␣-chain, has an enhanced homology with the corresponding regions of IGF-1 (26,27). This results in a twofold increased IGF-1 receptor affinity relative to human insulin and in an increased competitive binding to IGF-1 receptors (26).…”

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confidence: 99%

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Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy

et al. 2003

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OBJECTIVE -To assess whether the insulin analog lispro may antagonize the renal effects of IGF-1, a mediator of glomerular hyperfiltration involved in the progression of diabetic and nondiabetic chronic nephropathies. RESEARCH DESIGN AND METHODS-In a randomized crossover study, we compared the renal and metabolic responses to regular or lispro insulin (0.1 units/kg body wt) administered after a euglycemic clamp and 5 and 30 min before a standard meal to 11 type 2 diabetic patients with macroalbuminuria.RESULTS -Two-and four-hour postprandial changes (vs. preprandial euglycemia) in glomerular filtration rate (GFR) followed a significantly different trend (5.8 Ϯ 5.0 vs. Ϫ6.3 Ϯ 4.7, P Ͻ 0.05; and 11.0 Ϯ 6.8 vs. 0.7 Ϯ 5.1%, P Ͻ 0.05) after regular insulin and lispro injection, respectively. After lispro, postprandial GFR changes were negatively correlated (r ϭ Ϫ0.48, P ϭ 0.0001) with plasma insulin concentration. After regular insulin, renal plasma flow increased in parallel with a decrease in renal vascular resistances. Both changes were fully prevented by lispro. Postprandial blood glucose maximum concentration (278 Ϯ 16 vs. 240 Ϯ 16 mg/dl, P Ͻ 0.01) and area under the curve (79,381 Ϯ 19,237 vs. 72,810 Ϯ 16,211 mg/dl per min, P Ͻ 0,05) were significantly lower after insulin lispro than after regular insulin injection, respectively, despite comparable postprandial insulin profiles. Changes in total and gluconeogenic amino acids followed a similar trend. Changes in blood glucose and plasma amino acids did not correlate with concomitant changes in GFR.CONCLUSIONS -In overt nephropathy of type 2 diabetes, lispro prevents glomerular hyperfiltration and offsets the renal effects of meal or meal-associated hyperglycemia by mechanisms possibly related to IGF-1 antagonism. Diabetes Care 26:502-509, 2003

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Section: Metabolic Studiessupporting

confidence: 82%

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confidence: 99%

Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy

et al. 2003

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“…Additionally, the analog was virtual ly identical to insulin in all in vitro assessments of insulin action [16]. The affinity of LysPro-insulin for the insulin receptor as measured in IM-9 lymphocytes was indistin guishable from that of human insulin.…”

Section: Lyspro-lnsulin Biologymentioning

confidence: 93%

Preparation of an Insulin with Improved Pharmacokinetics Relative to Human Insulin through Consideration of Structural Homology with Insulin-Like Growth Factor I

et al. 1994

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The Diabetes Control and Complications Trial has emphasized the need for improved control of blood glucose as a means to diminish long-term complications of diabetes. LysPro-insulin is an analog of human insulin whose design was modeled on structural homology with insulin-like growth factor I. An analysis of the structural conformation of insulin suggested that an inversion of amino acids B28 and B29 in the C-terminus of the B chain could yield an insulin analog with a faster onset of biological action. This insulin analog has proved to be virtually identical to human insulin in action, with one important exception. LysPro-insulin has demonstrated an improved time course of action in control of a mealtime glucose elevation. This offers the opportunity for improved convenience and safety for patients with insulin-dependent diabetes mellitus.

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“…In terms of activity on lipogenesis, insulin lispro was found to be essentially the same as human insulin [64]. Pharmacokinetic studies indicate that insulin lispro acts within 15 min, peaks in approximately 1 hrs and disappears within 2-4 hrs after SC injection [67,70]. In clinical studies, as expected from a short-acting analogue, insulin lispro achieved signifi cant improvements in postprandial glucose levels with a lower rate of hypoglycaemic events compared with regular insulin [71][72][73].…”

Section: Scientifi C Informationmentioning

confidence: 99%

Review of insulin and its analogues in diabetes mellitus

Mane¹,

Chaluvaraju²,

Niranjan³

et al. 2012

J Basic Clin Pharma

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DIABETES MELLITUSD iabetes mellitus (DM) is a metabolic disorder resulting from a defect in insulin secretion, insulin action or both [1][2][3][4]. Insulin defi ciency in turn leads to chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism [1][2][3][4]. As the disease progresses tissue or vascular damage ensues leading to severe diabetic complications such as retinopathy [5,6], neuropathy [7,8], nephropathy [9,10], Cardiovascular complications [11,12] and ulceration [13,14]. Th us diabetes covers a wide range of heterogeneous diseases. Diabetes is the most common endocrine disorder and by the year 2010, it was estimated that more than 200 million people worldwide had DM and 300 million will subsequently have the disease by 2025 [15][16][17]. Th e diagnostic criteria and the classifi cation of diabetes was fi rst put forward by the World Health Organization (WHO) in 1965[18] then by the National Diabetes Data Group (NDDG) in 1979 [19] and this was followed by simplifi ed recommendations by the WHO in 1980 [20]. Th ese WHO recommendations were modifi ed slightly in 1985 [21]. Th e latest recommendations have been published by the American Diabetes Association (ADA) in 1997 and by the WHO in 1999. Both groups agree on the recommendations and criteria [2,22].According to the ADA recommendation changes in 1997, the fasting glucose concentration should be used in routine screening for diabetes as well as epidemiological studies; the threshold for fasting glucose was changed from 7.8 mmol/L (140 mg/dl) to 7.0 mmol/L (126 mg/dl); however the 2 hrs glucose criterion remains as 11.1 mmol/L (200 mg/dL). For the diagnosis of diabetes, at least one of the below criteria must apply. Th e WHO diagnosis and classifi cation of diabetes mellitus (1999) are identical to those of ADA, a fasting glucose = 7.0 mmol/L (126 mg/dl) and /or a 2 hrs glucose = 11.1 mmol/L (200 mg/dL). Th e report states that diagnosis should not be based on a single glucose determination but requires confi rmatory symptoms or blood/plasma determination. Ideally therefore, both the 2 hrs and fasting value should be used. Th ese recommendations contrast with those of ADA Expert Committee which gives primacy to the fasting plasma glucose. Th e WHO classifi cation includes both clinical stages (normoglycaemia, impaired glucose tolerance/impaired fasting glucose (IGT/IFG), diabetes and aetiological types of diabetes mellitus, identical to the ADA except that WHO group includes classifi cation formerly known as gestational impaired glucose tolerance (GIGT) and GDM: fasting glucose = 7.0 mmol/L (126 mg/dL) and/or 2 hrs glucose = 7.8 mmol/ L (140 mg/dL) after a 75-g OGTT.Diabetes mellitus may be categorized into several types but the two major types are type I and type II [21,23]. On the basis of aetiology, the term type I and type II were widely used to describe IDDM and NID-DM, respectively. Th e term juvenile -onset diabetes has sometimes been used for IDDM and maturity-onset for NIDDM.Type I (Ia, Ib) ß-cell destruction with litt...

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Insulin and IGF-I analogs: novel approaches to improved insulin pharmacokinetics

Cited by 7 publications

References 5 publications

Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy

Renal and Metabolic Effects of Insulin Lispro in Type 2 Diabetic Subjects With Overt Nephropathy

Preparation of an Insulin with Improved Pharmacokinetics Relative to Human Insulin through Consideration of Structural Homology with Insulin-Like Growth Factor I

Review of insulin and its analogues in diabetes mellitus

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